p27 deregulation in breast cancer: Prognostic significance and implications for therapy

Journal of Mammary Gland Biology and Neoplasia

Volumn 9, Issue 1, 2004, Pages 67-80

  Alkarain, A ^a   Jordan, R ^b   Slingerland, J ^a,c  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF MIAMI   (United States)

Author keywords

Breast cancer; Cell cycle; p27; Prognosis; Signal transduction

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 2 MORPHOLINO 8 PHENYLCHROMONE; ANTIESTROGEN; ANTINEOPLASTIC AGENT; AROMATASE INHIBITOR; CYCLIN D; CYCLIN DEPENDENT KINASE 2; CYCLIN E; CYCLOPHOSPHAMIDE; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ESTROGEN RECEPTOR; FLUOROURACIL; METHOTREXATE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PROTEIN P27; PROTEIN TYROSINE KINASE INHIBITOR; RAS PROTEIN; TAMOXIFEN; UNCLASSIFIED DRUG;

BREAST CANCER; CANCER CHEMOTHERAPY; CANCER DIAGNOSIS; CANCER GRADING; CANCER THERAPY; CELL ADHESION; CELL CYCLE G1 PHASE; CELL CYCLE S PHASE; CELL DIFFERENTIATION; CLINICAL TRIAL; CYTOPLASM; DEREGULATION; DRUG RECEPTOR BINDING; GENE ACTIVATION; GENE MUTATION; HISTOPATHOLOGY; HUMAN; PROGNOSIS; PROTEIN DEGRADATION; PROTEIN DEPLETION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REGULATORY MECHANISM; REVIEW; SCORING SYSTEM; SIGNAL TRANSDUCTION; STAINING; TUMOR CELL; TUMOR DIFFERENTIATION;

BREAST NEOPLASMS; CELL ADHESION; CELL CYCLE; CELL CYCLE PROTEINS; CELL TRANSFORMATION, NEOPLASTIC; CYCLIN-DEPENDENT KINASE INHIBITOR P27; ENZYME INHIBITORS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, TUMOR SUPPRESSOR; HUMANS; PROGNOSIS; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS;

EID: 4344637857     PISSN: 10833021     EISSN: None     Source Type: Journal    
DOI: 10.1023/B:JOMG.0000023589.00994.5e     Document Type: Review

References (152)

1. C. J. Sherr (1994). G1 phase progression: Cycling on cue. Cell 79:551-555.
2. C. J. Sherr and J. M. Roberts (1995). Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 9:1149-1163.
3. S. I. Reed, E. Bailly, V. Dulic, L. Hengst, D. Resnitzky, and J. Slingerland (1994). G1 control in mammalian cells. J. Cell Sci. 18(Suppl.):69-73.
4. C. J. Sherr and J. M. Roberts (1999). CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 13:1501-1512.
5. J. Slingerland and M. Pagano (2000). Regulation of the cdk inhibitor p27 and its deregulation in cancer. J. Cell Physiol. 183:10-17.
6. J. LaBaer, M. D. Garrett, L. F. Stevenson, J. M. Slingerland, C. Sandhu, H. S. Chou, A. Fattaey, and E. Harlow (1997). New functional activities for the p21 family of CDK inhibitors. Genes Dev. 11:847-862.
7. M. Cheng, P. Olivier, J. A. Diehl, M. Fero, M. F. Roussel, J. M. Roberts, and C. J. Sherr (1999). The p21(Cip1) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J. 18:1571-1583.
8. A. Koff, M. Ohtsuki, K. Polyak, J. M. Roberts, and J. Massague (1993). Negative regulation of G1 in mammalian cells: Inhibition of cyclin E-dependent kinase by TGF-beta. Science 260:536-539.
9. L. Hengst, V. Dulic, J. M. Slingerland, E. Lees, and S. I. Reed (1994). A cell cycle-regulated inhibitor of cyclin-dependent kinases. Proc. Natl. Acad. Sci. U.S.A. 91:5291-5295.
10. K. Polyak, J. Y. Kato, M. J. Solomon, C. J. Sherr, J. Massague, J. M. Roberts, and A. Koff (1994). p27Kip1, a cyclin-inhibitor. Cdk, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev. 8:9-22.
11. J. M. Slingerland, L. Hengst, C. H. Pan, D. Alexander, M. R. Stampfer, and S. I. Reed (1994). A novel inhibitor of cyclin-Cdk activity detected in transforming growth factor β-arrested epithelial cells. Mol. Cell Biol. 14:3683-3694.
12. L. Hengst and S. I. Reed (1996). Translational control of p27Kip1 accumulation during the cell cycle. Science 271:1861-1864.
13. Q. M. Wang, J. B. Jones, and G. P. Studzinski (1996). Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL-60 cells. Cancer Res. 56:264-267.
14. B. Durand, F. B. Gao, and M. Raff (1997). Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J. 16:306-317.
15. H. Koyama, E. W. Raines, K. E. Bornfeldt, J. M. Roberts, and R. Ross (1996). Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors. Cell 87:1069-1078.
16. St. B. Croix, V. Florenes, A. Rak, J. W. Flanagan, N. Bhattacharya, J. M. Slingerland, and R. S. Kerbel (1996). Impact of the cyclin dependent kinase inhibitor p27Kip1 on adhesion-dependent resistance of tumor cells to anticancer agents. Nat. Med. 2:1204-1210.
17. N. Watanabe, T. Hunter, and E. Ruoslahti (1996). Dependence of cyclin E-cdk2 kinase activity on cell anchorage. Science 271:499-502.
18. F. Fang, G. Orend, N. Watanabe, T. Hunter, and E. Ruoslahti (1996). Dependence of cyclin E-CDK2 kinase activity on cell anchorage. Science 271:499-502.
19. R. K. Assoian (1997). Anchorage-dependent cell cycle progression. J. Cell Biol. 136:1-3.
20. G. Radeva, T. Petrocelli, E. Behrend, C. Leung-Hagesteijn, J. Filmus, J. Slingerland, and S. Dedhar (1997). Overexpression of the integrin-linked kinase promotes anchorage-independent cell cycle progression. J. Biol. Chem. 272:13937-13944.
21. R. J. Sheaff, M. Groudine, M. Gordon, J. M. Roberts, and B. E. Clurman (1997). Cyclin E-CDK2 is a regulator of p27Kip1. Genes Dev. 11:1464-1478.
22. J. Vlach, S. Hennecke, and B. Amati (1997). Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27. EMBO J. 16:5334-5344.
23. S. Ciarallo, V. Subramaniam, W. Hung, J. H. Lee, R. Kotchetkov, C. Sandhu, A. Milic, and J. M. Slingerland (2002). Altered p27(Kip1) phosphorylation, localization, and function in human epithelial cells resistant to transforming growth factor beta-mediated G(1) arrest. Mol. Cell Biol. 22:2993-3002.
24. S. S. Millard, J. S. Yan, H. Nguyen, M. Pagano, H. Kiyokawa, and A. Koff (1997). Enhanced ribosomal association of p27(Kip1) mRNA is a mechanism contributing to accumulation during growth arrest. J. Biol. Chem. 272:7093-7098.
25. U. Gopfert, M. Kullmann, and L. Hengst (2003). Cell cycle-dependent translation of p27 involves a responsive element in its 5′-UTR that overlaps with a uORF. Hum. Mol. Genet. 12:1767-1779.
26. M. Kullmann, U. Gopfert, B. Siewe, and L. Hengst (2002). Elav/Hu proteins inhibit p27 translation through an IRES element in the p27 5′ UTR. Genes & Development 16:3087-3099.
27. M. Pagano, S. W. Tam, A. M. Theodoras, P. Beer-Romero, G. Del. Sal, V. Chau, P. R. Yew, G. F. Draetta, and M. Rolfe (1995). Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269:682-685.
28. N. P. Malek, H. Sundberg, S. McGrew, K. Nakayama, T. R. Kyriakidis, and J. M. Roberts (2001). A mouse knock-in model exposes sequential proteolytic pathways that regulate p27Kip1 in G1 and S phase. Nature 413:323-327.
29. M. K. Connor, R. Kotchetkov, S. Cariou, A. Resch, R. Lupetti, R. G. Beniston, F. Melchior, L. Hengst, and J. M. Slingerland (2003). CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis. Mol. Biol. Cell. 14:201-213.
30. Y. Zeng, K. Hirano, M. Hirano, J. Nishimura, and H. Kanaide (2000). Minimal requirements for the nuclear localization of p27Kip1, a cyclin-dependent kinase inhibitor. Biochem. Biophys. Res. Commun. 274:37-42.
31. T. Guan, R. H. Kehlenbach, E. C. Schirmer, A. Kehlenbach, F. Fan, B. E. Clurman, N. Arnheim, and L. Gerace (2000). Nup50, a nucleoplasmically oriented nucleoporin with a role in nuclear protein export. Mol. Cell Biol. 20:5619-5630.
32. D. Muller, K. Thieke, A. Burgin, A. Dickmanns, and M. Eilers (2000). Cyclin E mediated elimination of p27 requires its interaction with the nuclear poreassociated protein mNPAP60. EMBO J. 19:2169-2180.
33. M. Boehm, T. Yoshimoto, M. F. Crook, S. Nallamshetty, A. True, G. J. Nabel, and E. G. Nabel (2002). A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression. EMBO J. 21:3390-3401.
34. G. Rodier, A. Montagnoli, L. Di. Marcotullio, P. Coulombe, G. F. Draetta, M. Pagano, and S. Meloche (2001). p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis. EMBO J. 20:6672-6682.
35. A. Montagnoli, F. Fiore, E. Eytan, A. C. Carrano, G. F. Draetta, A. Hershko, and M. Pagano (1999). Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation. Genes Dev. 13:1181-1189.
36. T. Ohta, J. J. Michel, A. J. Schottelius, and Y. Xiong (1999). T. ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol. Cell. 3:535-541.
37. A. C. Carrano, E. Eytan, A. Hershko, and M. Pagano (1999). SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat. Cell Biol. 1:193-199.
38. L. M. Tsvetkov, K. H. Yeh, S. J. Lee, H. Sun, and H. Zhang (1999). p27(Kip1) ubiquitination and degradation is regulated (Skp2) complex through phosphorylated Thr187 in p27. Curr. Biol. 9:661-664.
39. H. Sutterluty, E. Chatelain, A. Marti, C. Wirbelauer, M. Senften, U. Muller, and W. Krek (1999). p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells. Nat. Cell Biol. 1:207-214.
40. C. Spruck, H. Strohmaier, M. Watson, A. P. Smith, A. Ryan, T. W. Krek, and S. I. Reed (2001). A CDK-independent function of mammalian Cks1: Targeting of SCF(Skp2) to the CDK inhibitor p27Kip1. Mol. Cell. 7:639-650.
41. D. Ganoth, G. Bornstein, T. K. Ko, B. Larsen, M. Tyers, M. Pagano, and A. Hershko (2001). The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27. Nat. Cell Biol. 3:321-324.
42. T. Hara, T. Kamura, K. Nakayama, K. Oshikawa, S. Hatakeyama, and K. I. Nakayama (2001). Degradation of p27Kip1 at the G0-G1 transition mediated by a Skp2-independent ubiquitination pathway. J. Biol. Chem. 276:48937-48943.
43. H. Aktas, H. Cai, and G. M. Cooper (1997). Ras links growth factor signaling to the cell cycle machinery via regulation of cyclin D1 and the Cdk inhibitor p27KIP1. Mol. Cel. Biol. 17:3850-3857.
44. M. Kawada, S. Yamagoe, Y. Murakami, K. Suzuki, S. Mizuno, and Y. Uehara (1997). Induction of p27Kip1 degradation and anchorage independence by Ras through the MAP kinase signaling pathway. Oncogene 15:629-637.
45. N. Takuwa and Y. Takuwa (1997). Ras activity late in G1 phase required for p27kip1 downregulation, passage through point. the. restriction, and entry into S phase in growth factor-stimulated NIH 3T3 fibroblasts. Mol. Cell Biol. 17:5348-5358.
46. R. Hoshino, S. Tanimura, K. Watanabe, T. Kataoka, and M. Kohno (2001). Blockade of the extracellular signal-regulated kinase pathway induces marked G1 cell cycle arrest and apoptosis in tumor cells in which the pathway is constitutively activated: Up-regulation of p27(Kip1). J. Biol. Chem. 276:2686-2692.
47. M. D. Pegram, G. Pauletti, and D. J. Slamon (1998). HER-2/neu as a predictive marker of response to breast cancer therapy. Breast Cancer Res. Treat. 52:65-77.
48. D. J. Slamon, G. M. Clark, S. G. Wong, W. J. Levin, A. Ullrich, and W. L. McGuire (1987). Human breast cancer: Correlation of relapse and survival with amplification of the Her-2/Neu oncogene. Science 235:177-182.
49. D. J. Slamon, W. Godolphin, L. A. Jones, J. A. Holt, S. G. Wong, D. E. Keith, W. J. Levin, S. G. Stuart, J. Udove, and A. Ullrich (1989). Studies of the Her-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707-712.
50. J. G. Klijn, P. M. Berns, P. I. Schmitz, and J. A. Foekens (1992). The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients. Endocr. Rev. 13:3-17.
51. V. Pawlowski, F. Revillion, M. Hebbar, L. Hornez, and J. P. Peyrat (2000). Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. Clin. Cancer Res. 6:4217-4225.
52. A. E. Lenferink, D. Busse, W. M. Flanagan, F. M. Yakes, and C. L. Arteaga (2001). ErbB2/neu kinase modulates cellular p27(Kip1) and cyclin D1 through multiple signaling pathways. Cancer Res. 61:6583-6591.
53. H. Y. Yang, B. P. Zhou, M. C. Hung, and M. H. Lee (2000). Oncogenic signals of HER-2/neu in regulating the stability of the cyclin-dependent kinase inhibitor p27. J. Biol. Chem. 275:24735-24739.
54. J. C. Donovan, A. Milic, and J. M. Slingerland (2001). Constitutive MEK/MAPK activation leads to p27Kip1 deregulation and antiestrogen resistance in human breast cancer cells. J. Biol. Chem. 276:40888-40895.
55. L. Newman, W. Xia, H. Y. Yang, A. Sahin, M. Bondy, F. Lukmanji, M. C. Hung, and M. H. Lee (2001). Correlation of p27 protein expression with HER-2/neu expression in breast cancer. Mol. Carcinog. 30:169-175.
56. V. J. Spataro, H. Litman, G. Viale, F. Maffini, M. Masullo, R. Golouh, F. J. Martinez-Tello, P. Grigolato, K. B. Shilkin, B. A. Gusterson, M. Castiglione-Gertsch, K. Price, J. Lindtner, H. Cortes-Funes, E. Simoncini, M. J. Byrne, J. Collins, R. D. Gelber, A. S. Coates, and A. Goldhirsch (2003). Decreased immunoreactivity for p27 protein in patients with early-stage breast carcinoma is correlated with HER-2/neu overexpression and with benefit from one course of perioperative chemotherapy in patients with negative lymph node status: Results from International Breast Cancer Study Group Trial V. Cancer 97:1591-1600.
57. H. A. Lane, I. Beuvink, A. B. Motoyama, J. M. Daly, R. M. Neve, and N. E. Hynes (2000). ErbB2 potentiates breast tumor proliferation through modulation of p27(Kip1)-Cdk2 complex formation receptor overexpression does not determine growth dependency. Mol. Cell Biol. 20:3210-3223.
58. A. Alessandrini, D. S. Chiaur, R. Erikson, and M. Pagano (1997). Regulation of the cyclin-depedent kinase inhibitor p27 by degradation and phosphorylation. Leukemia 11:342-345.
59. N. Ishida, M. Kitagawa, S. Hatakeyama, and K. Nakayama (2000). Phosphorylation at Serine 10, a major phosphorylation site of p27Kip1, increases its protein stability. J. Biol. Chem. 275:25146-25154.
60. X. Liu, Y. Sun, M. Ehrlich, T. Lu, Y. Kloog, R. A. Weinberg, H. F. Lodish, and Y. I. Henis (2000). Disruption of TGF-beta growth inhibition by oncogenic ras is linked to p27Kip1 mislocalization. Oncogene 19:5926-5935.
61. A. Hirai, S. Nakamura, Y. Noguchi, T. Yasuda, M. Kitagawa, I. Tatsuno, T. Oeda, K. Tahara, T. Terano, S. Narumiya, L. D. Kohn, and Y. Saito (1997). Geranylgeranylated rho small GTPase(s) are essential for the degradation of p27Kip1 and facilitate the progression from G1 to S phase in growth-stimulated rat FRTL-5 cells. J. Biol. Chem. 272:13-16.
62. J. D. Weber, W. Hu, S. C. Jefcoat Jr., D. M. Raben, and J. J. Baldassare (1997). Ras-stimulated extracellular signal-related kinase 1 and RhoA activities coordinate platelet-derived growth factor-induced G1 progression through the independent regulation of cyclin D1 and p27. J. Biol. Chem. 272:32966-32971.
63. W. Hu, C. J. Bellone, and J. J. Baldassare (1999). RhoA stimulates p27(Kip) degradation through its regulation of cyclin E/CDK2 activity. J. Biol. Chem. 274:3396-3401.
64. I. Shin, F. M. Yakes, F. Rojo, N. Y. Shin, A. V. Bakin, J. Baselga, and C. L. Arteaga (2002). PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat. Med. 8:1145-1152.
65. G. Viglietto, M. L. Motti, P. Bruni, R. M. Melillo, A. D'Alessio, D. Califano, F. Vinci, G. Chiappetta, P. Tsichlis, A. Bellacosa, A. Fusco, and M. Santoro (2002). Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. Nat. Med. 8:1136-1144.
66. J. Liang, J. Zubovitz, T. Petrocelli, R. Kotchetkov, M. K. Connor, K. Han, J. H. Lee, S. Ciarallo, C. Catzavelos, R. Beniston, E. Franssen, and J. M. Slingerland (2002). PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat. Med. 8:1153-1160.
67. L. P. Weng, J. L. Brown, and C. Eng (2001). PTEN coordinates G(1) arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model. Hum. Mol. Genet. 10:599-604.
68. Y. Narita, M. Nagane, K. Mishima, H. J. Huang, F. B. Furnari, and W. K. Cavenee (2002). Mutant epidermal growth factor receptor signaling down-regulates p27 through activation of the phosphatidylinositol 3-kinase/Akt pathway in glioblastomas. Cancer Res. 62:6764-6769.
69. F. M. Yakes, W. Chinratanalab, C. A. Ritter, W. King, S. Seelig, and C. L. Arteaga (2002). Herceptin-induced inhibition of phosphatidylinositol-3 kinase and Akt Is required for antibody-mediated effects on p27, cyclin D1, and antitumor action. Cancer Res. 62:4132-4141.
70. F. Gesbert, W. R. Sellers, S. Signoretti, M. Loda, and J. D. Griffin (2000). BCR/ABL regulates expression of the cyclin-dependent kinase inhibitor p27Kip1 through the phosphatidylinositol 3-kinase/AKT pathway. J. Biol. Chem. 275:39223-39230.
71. H. Murillo, H. Huang, L. J. Schmidt, D. I. Smith, and D. J. Tindall (2001). Role of PI3K signaling in survival and progression of LNCaP prostate cancer cells to the androgen refractory state. Endocrinology 142:4795-4805.
72. F. L. Forti, T. T. Schwindt, M. S. Moraes, C. B. Eichler, and H. A. Armelin (2002). ACTH promotion of p27(Kip1) induction in mouse y1 adrenocortical tumor cells is dependent on both pka activation and Akt/PKB inactivation. Biochemistry 41:10133-10140.
73. R. Mamillapalli, N. Gavrilova, V. T. Mihaylova, L. M. Tsvetkov, H. Wu, H. Zhang, and H. Sun (2001). PTEN regulates the ubiquitin-dependent degradation of the CDK inhibitor p27(KIP1) through the ubiquitin E3 ligase SCF(SKP2). Curr. Biol. 11:263-267.
74. C. Wirbelauer, H. Sutterluty, M. Blondel, M. Gstaiger, M. Peter, F. Reymond, and W. Krek (2000). The F-box protein Skp2 is a ubiquitylation target of a Cul1-based core ubiquitin ligase complex: Evidence for a role of Cul1 in the suppression of Skp2 expression in quiescent fibroblasts. EMBO J. 19:5362-5375.
75. G. Yang, G. Ayala, A. D. Marzo, W. Tian, A. Frolov, T. M. Wheeler, T. C. Thompson, and J. W. Harper (2002). Elevated Skp2 protein expression in human prostate cancer: Association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival. Clin. Cancer Res. 8:3419-3426.
76. E. J. McManus and D. R. Alessi (2002). TSC1-TSC2: A complex tale of PKB-mediated S6K regulation. Nat. Cell Biol. 4:E214-E216.
77. S. J. Marygold and S. J. Leevers (2002). Growth signaling: TSC takes its place. Curr. Biol. 12:R785-R787.
78. T. Soucek, R. S. Yeung, and M. Hengstschlager (1998). Inactivation of the cyclin-dependent kinase inhibitor p27 upon loss of the tuberous sclerosis complex gene-2. Proc. Natl. Acad. Sci. US.A. 95:15653-15658.
79. kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. Nature 372:570-573.
80. E. J. Firpo, A. Koff, M. J. Solomon, and J. M. Roberts (1994). Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of human T lymphocytes. Mol. Cell Biol. 14:4889-4901.
81. S. W. Blain and J. Massague (2002). Breast cancer banishes p27 from nucleus. Nat. Med. 8:1076-1078.
82. S. S. McAllister, M. Becker-Hapak, G. Pintucci, M. Pagano, and S. F. Dowdy (2003). Novel p27(kip1) C-terminal scatter domain mediates Rac-dependent cell migration independent of cell cycle arrest functions. Mol. Cell Biol. 23:216-228.
83. S. J. Moeller, E. D. Head, and R. J. Sheaff (2003). p27Kip1 inhibition of GRB2-SOS formation can regulate Ras activation. Mol. Cell Biol. 23:3735-3752.
84. Kip1. Genes Dev. 11:2335-2346.
85. H. Kiyokawa, R. D. Kineman, K. O. Manova-Todorova, V. C. Soares, E. S. Hoffman, M. Ono, D. Khanam, A. C. Hayday, L. A. Frohman, and A. Koff (1996). Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27Kip1. Cell 85:721-732.
86. K. Nakayama, N. Ishida, M. Shirane, A. Inomata, T. Inoue, N. Shishido, I. Horii, and D. Y. Loh (1996). Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 85:707-720.
87. M. L. Fero, M. Rivkin, M. Tasch, P. Porter, C. E. Carow, K. Polyak, E. Firpo, L. Tsai, V. Broudy, R. M. Perlmutter, K. Kaushansky, and J. M. Roberts (1996). A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis and female sterility in p27Kip1-deficient mice. Cell 85:733-744.
88. C. Cordon-Cardo, A. Koff, M. Drobnjak, P. Capodieci, I. Osman, S. S. Millard, P. B. Gaudin, M. Fazzari, ZF. Zhang, J. Massague, and H. I. Scher (1998). Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma. J. Natl. Cancer Inst. 90:1284-1291.
89. M. L. Fero, E. Randel, K. E. Gurley, J. M. Roberts, and C. J. Kemp (1998). The murine gene p27Kip1 is haplo-insufficient for tumour suppression. Nature 396:177-180.
90. P. J. Hauser, D. Agrawal, M. Flanagan, and W. J. Pledger (1997). The role of p27kip1 in the in vitro differentiation of murine keratinocytes. Cell Growth Differ. 8:203-211.
91. B. L. Harvat, A. Wang, P. Seth, and A. M. Jetten. Up-regulation of p27Kip1, p21WAF1/Cip1 and p16Ink4a is associated with, but not sufficient for, induction of squamous differentiation. J. Cell Sci. 1998;111(Pt. 9):1185-1196.
92. G. Baldassarre, B. Belletti, P. Bruni, A. Boccia, F. Trapasso, F. Pentimalli, M. V. Barone, G. Chiappetta, MT. Vento, S. Spiezia, A. Fusco, and G. Viglietto (1999). Overexpressed cyclin D3 contributes to retaining the growth inhibitor p27 in the cytoplasm of thyroid tumor cells. J. Clin. Invest. 104:865-874.
93. C. Catzavelos, N. Bhattacharya, Y. C. Ung, J. A. Wilson, L. Roncari, C. Sandhu, P. Shaw, H. Yeger, I. Morava-Protzner, L. Kapusta, E. Franssen, K. I. Pritchard, and J. M. Slingerland (1997). Decreased levels of the cell-cycle inhibitor p27Kip1 protein: Prognostic implications in primary breast cancer. Nat. Med. 3:227-230.
94. S. Fredersdorf, J. Burns, A. M. Milne, G. Packham, L. Fallis, C. E. Gillett, J. A. Royds, D. Peston, P. A. Hall, AM. Hanby, D. M. Barnes, S. Shousha, M. J. O'Hare, and X. Lu (1997). High level expression of p27(kip1) and cyclin D1 in some human breast cancer cells: Inverse correlation between the expression of p27(kip1) and degree of malignancy in human breast and colorectal cancers. Proc. Natl. Acad. Sci. U.S.A. 94:6380-6385.
95. C. E. Gillett, P. Smith, G. Peters, X. Lu, and D. M. Barnes (1999). Cyclin-dependent kinase inhibitor p27Kip1 expression and interaction with other cell cycle-associated proteins in cmammary arcinoma. J. Pathol. 187:200-206.
96. J. Wu, Z. Z. Shen, J. S. Lu, M. Jiang, Q. X. Han, J. A. Fontana, S. H. Barsky, and Z. M. Shao (1999). Prognostic role of p27Kip1 and apoptosis in human breast cancer. Br. J. Cancer. 79:1572-1578.
97. W. Reed, V. A. Florems, R. Holm, E. Hannisdal, and J. M. Nesland (1999). Elevated levels of p27, p21 and cyclin D1 correlate with positive oestrogen and progesterone receptor status in node-negative breast carcinoma patients. Virchows Arch. 435:116-124.
98. A. Tsuchiya, G. J. Zhang, and M. Kanno (1999). Prognostic impact of cyclin-dependent kinase inhibitor p27kip1 in node-positive breast cancer. J. Surg. Oncol. 70:230-234.
99. S. Han, K. Park, H. Y. Kim, M. S. Lee, H. J. Kim, and Y. D. Kim (1999). Reduced expression of p27Kip1 protein is associated with poor clinical outcome of breast cancer patients treated with systemic chemotherapy and is linked to cell proliferation and differentiation. Breast Cancer Res. Treat. 55:161-167.
100. M. Barbareschi, H. van Tinteren, F. A. Mauri, S. Veronese, H. Peterse, P. Maisonneuve, O. Caffo, M. Scaioli, C. Doglioni, E. Galligioni, P. P. Dalla, and R. Michalides (2000). p27(kip1) expression in breast carcinomas: An immunohistochemical study on 512 patients with long-term follow-up. Int. J. Cancer. 89:236-241.
101. P. O. Chappuis, L. Kapusta, L. R. Begin, N. Wong, J. S. Brunet, S. A. Narod, J. Slingerland, and W. D. Foulkes (2000). Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer. J. Clin. Oncol. 18:4045-4052.
102. M. Leivonen, S. Nordling, J. Lundin, K. von Boguslawski, and C. Haglund (2001). p27 expression correlates with short-term, but not with long-term prognosis in breast cancer. Breast Cancer Res. Treat. 67:15-22.
103. J. T. Winston, S. R. Coats, Y-Z. Wang, and W. J. Pledger (1996). Regulation of the cell cycle machinery by oncogenic ras. Oncogene 12:127-134.
104. J. Y. Kato, M. Matsuoka, K. Polyak, J. Massague, and C. J. Sherr (1994). Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation. Cell 79:487-496.
105. X. Zhu, M. Ohtsubo, R. M. Bohmer, J. M. Roberts, and R. K. Assoian (1996). Adhesion-dependent cell cycle progression linked to the expression of cyclin D1, activation of cyclin E-cdk2, and phosphorylation of the retinoblastoma protein. J. Cell Biol. 133:391-403.
106. J. Folkman and A. Moscona (1978). Role of cell shape in growth control. Nature 273:345-349.
107. K. F. Becker, M. J. Atkinson, U. Reich, I. Becker, H. Nekarda, J. R. Siewert, and H. Hofler (1994). E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 54:3845-3852.
108. G. Berx, A. M. Cleton-Jansen, K. Strumane, W. J. de Leeuw, F. Nollet, F. van Roy, and C. Cornelisse (1996). E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene 13:1919-1925.
109. J. Behrens, J. P. von Kries, M. Kuhl, L. Bruhn, D. Wedlich, R. Grosschedl, and W. Birchmeier (1996). Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 382:638-642.
110. M. Molenaar, W. M. van de, M. Oosterwegel, J. Peterson-Maduro, S. Godsave, V. Korinek, J. Roose, O. Destree, and H. Clevers (1996). XTcf-3 transcription factor mediates betacatenin-induced axis formation in Xenopus embryos. Cell 86:391-399.
111. O. Huber, R. Korn, J. McLaughlin, M. Ohsugi, B. G. Herrmann, and R. Kemler (1996). Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech. Dev. 59:3-10.
112. Kip1 in human malignancies. Cancer Res. 55:2266-2269.
113. Kip1 gene to 12p13 and its analysis in luekemias. Cancer Res. 55:1206-1210.
114. Kip1: Chromosomal mapping to 12p12-12p13.1 and absence of mutations in human tumours. Cancer Res. 55:1211-1214.
115. G. Viglietto and A. Fusco (2002). Understanding p27(kip1) deregulation in cancer: Down-regulation or mislocalization? Cell Cycle. 1:394-400.
116. M. Loda, B. Cukor, S. W. Tam, P. Lavin, M. Fiorentino, G. F. Draetta, J. M. Jessup, and M. Pagano (1997). Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat. Med. 3:231-234.
117. P. Tan, B. Cady, M. Wanner, P. Worland, B. Cukor, C. Magi-Galluzzi, P. Lavin, G. Draetta, M. Pagano, and M. Loda (1997). The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. Cancer Res. 57:1259-1263.
118. V. Esposito, A. Baldi, A. De. Luca, A. M. Groger, M. Loda, G. G. Giordano, M. Caputi, F. Baldi, M. Pagano, and A. Giordano (1997). Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer. Cancer Res. 57:3381-3385.
119. S. P. Singh, J. Lipman, H. Goldman, F. H. Ellis, L. Aizenman, M. G. Cangi, S. Signoretti, D. S. Chiaur, M. Pagano, and M. Loda (1998). Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma. Cancer Res. 58:1730-1735.
120. R. Chiarle, L. Budel, J. Skolnik, G. Frizzera, M. Chilosi, A. Corato, G. Pizzolo, J. Magidson, A. Montagnoli, M. Pagano, B. Maes, C. DeWolf, and G. Inghirani (in press). Increased proteasome degradation of cyclin-dependent kinase inhibitor p27 is associated with a decreased overall survival in mantle cell lymphoma. Blood.
121. D. Hershko, G. Bornstein, O. Ben. Izhak, A. Carrano, M. Pagano, M. M. Krausz, and A. Hershko (2001). Inverse relation between levels of p27(Kip1) and of its ubiquitin ligase subunit Skp2 in colorectal carcinomas. Cancer 91:1745-1751.
122. Y. Kudo, S. Kitajima, S. Sato, M. Miyauchi, I. Ogawa, and T. Takata (2001). High expression of S-phase kinase-interacting protein 2, human F-protein. box, correlates with poor prognosis in oral squamous cell carcinomas. Cancer Res. 61:7044-7047.
123. E. Latres, R. Chiarle, B. A. Schulman, N. P. Pavletich, A. Pellicer, G. Inghirami, and M. Pagano (2001). Role of the F-box protein Skp2 in lymphomagenesis. Proc. Natl. Acad. Sci. U.S.A. 98:2515-2520.
124. S. Yokoi, K. Yasui, Saito-F. Ohara, K. Koshikawa, T. Iizasa, T. Fujisawa, T. Terasaki, A. Horii, T. Takahashi, S. Hirohashi, and J. Inazawa (2002). A novel target gene, SKP2, within the 5p13 amplicon that is frequently detected in small cell lung cancers. Am. J. Pathol. 161:207-216.
125. T. A. Masuda, H. Inoue, H. Sonoda, S. Mine, Y. Yoshikawa, K. Nakayama, K. Nakayama, and M. Mori (2002). Clinical and biological significance of S-phase kinase-associated protein 2 (Skp2) gene expression in gastric carcinoma: Modulation of malignant phenotype by Skp2 overexpression, possibly via p27 proteolysis. Cancer Res. 62:3819-3825.
126. M. Gstaiger, R. Jordan, M. Lim, C. Catzavelos, J. Mestan, J. Slingerland, and W. Krek (2001). Skp2 is oncogenic and overexpressed in human cancers. Proc. Natl. Acad. Sci. U.S.A. 98:5043-5048.
127. Kip1. Breast Cancer Restreat 52:29-41.
128. P. L. Porter, K. E. Malone, P. J. Heagerty, G. M. Alexander, L. A. Gatti, E. J. Firpo, J. R. Daling, and J. M. Roberts (1997). Expression of cell cycle regulators p27kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. Nat. Med. 3:222-225.
129. M. Loden, N. H. Nielsen, G. Roos, S. O. Emdin, and G. Landberg (1999). Cyclin E dependent kinase activity in human breast cancer in relation to cyclin E, p27 and p21 expression and retinoblastoma protein phosphorylation. Oncogene 18:2557-2566.
130. F. De Paola, A. M. Vecci, A. M. Granato, M. Liverani, F. Monti, A. M. Innoceta, L. Gianni, L. Saragoni, M. Ricci, F. Falcini, D. Amadori, and A. Volpi (2002). p27/kip1 expression in normal epithelium, benign and neoplastic breast lesions. J. Pathol. 196:26-31.
131. T. Moriya, K. Sakamoto, H. Sasano, M. Kawanaka, H. Sonoo, T. Manabe, and J. Ito (2000). Immunohistochemical analysis of Ki-67, p53, p21, and p27 in benign and malignant apocrine lesions of the breast: Its correlation to histologic findings in 43 cases. Mod. Pathol. 13:13-18.
132. R. A. Soslow, D. L. Carlson, M. G. Horenstein, and M. P. Osborne (2000). A comparison of cell cycle markers in well-differentiated lobular and ductal carcinomas. Breast Cancer Res. Treat. 61:161-170.
133. A. C. K. Leong, A. M. Hanby, H. W. W. Potts, D. S. P. Tan, D. Skilton, K. Ryder, W. H. Harris, R. D. Liebmann, D. M. Barnes, and C. E. Gillett (2000). Cell cycle proteins do not predict the outcome in grade I infiltrating ductal carcinoma of the breast. Int. J. Cancer. 89:26-31.
134. M. Barbareschi, O. Caffo, C. Doglioni, P. Fina, A. Marchetti, F. Buttitta, R. Leek, L. Morelli, E. Leonardi, G. Bevilacqua, P. Dalla Palma, and A. L. Harris (1996). p21WAF1 immunohistochemical expression in breast carcinoma: Correlations with clinicopathological data, oestrogen receptor status, MIB1 expression, p53 gene and protein alterations and relapse-free survival. Br. J. Cancer. 74:208-215.
135. R. M. Yang, J. Naitoh, M. Murphy, H. J. Wang, J. Philipson, J. B. deKernion, M. Loda, and R. E. Reiter (1998). Low p27 expression predicts poor disease-free survival in patients with prostate cancer. J. Urol. 159:941-945.
136. Kip1 is a novel prognostic factor in localized human prostate adenocarcinoma. Cancer Res. 58:542-548.
137. S. Masood (1995). Prediction of recurrence for advanced breast cancer. Traditional and contemporary pathologic and molecular markers. Surg. Oncol. Clin. N. Am. 4:601-632.
138. D. F. Hayes, C. Isaacs, and V. Stearns (2001). Prognostic factors in breast cancer: Current and new predictors of metastasis. J. Mammary Gland Biol. Neoplasia 6:375-392.
139. V. C. Jordan (1995). Studies on the estrogen receptor in breast cancer - 20 years as a target for the treatment and prevention of cancer. Breast Cancer Res. Treat. 36:267-285.
140. H. B. Muss, A. D.Thor, D. A. Berry, T. Kute, E. Liu, F. Koerner, C. T. Cirrincione, D. R. Budman, W. C. Wood, and M. Barcos (1994). c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N. Engl. J. Med. 330:1260-1268.
141. H. B. Muss, A. D. Thor, D. A. Berry, T. Kute, E. T. Liu, F. Koerner, C. T. Cirrincione, D. R. Budman, W. C. Wood, and M. Barcos (1994). c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer [published erratum appears in N. Engl. J. Med. 331(3):211, 1994.]. N. Engl. J. Med. 330:1260-1266.
142. K. Oka, Y. Suzuki, and T. Nakano (2000). Expression of p27 and p53 in cervical squamous cell carcinoma patients treated with radiotherapy alone: Radiotherapeutic effect and prognosis. Cancer 88:2766-2773.
143. F. Oshita, Y. Kameda, K. Nishio, G. Tanaka, K. Yamada, I. Nomura, H. Nakayama, and K. Noda (2000). Increased expression levels of
144. B. Fisher, J. P. Costantino, D. L. Wickerham, C. K. Redmond, M. Kavonah, and W. M. Cronin (1998). Tamoxifen for the prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1. J. Natl. Cancer Inst. 90:1371-1388.
145. L. Novotny, P. Rauko, A. Vachalkova, and M. Peterson-Biggs (2000). Tamoxifen in cancer therapy: Minireview. Neoplasma 47:3-7.
146. S. Cariou, J. C. Donovan, W. M. Flanagan, A. Milic, N. Bhattacharya, and J. M. Slingerland (2000). Down-regulation of p21WAF1/CIP1 or p27Kip1 abrogates antiestrogen-mediated cell cycle arrest in human breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 97:9042-9046.
147. A. S. Coutts and L. C. Murphy (1998). Elevated mitogen-activated protein kinase activity in estrogen-nonresponsive human breast cancer cells. Cancer Res. 58:4071-4074.
148. D. El-Ashry, D. Miller, S. Kharbanda, M. E. Lippman, and F. G. Kern (1997). Constitutive Raf-1 kinase activity in breast cancer cells induces both estrogen-independent growth and apoptosis. Oncogene 15:435.
149. H. Kurokawa, A. E. Lenferink, J. F. Simpson, P. I. Pisacane, M. X. Sliwkowski, J. T. Forbes, and C. L. Arteaga (2000). Inhibition of HER2/neu (erbB-2) and mitogen-activated protein kinases enhances tamoxifen action against HER2-overexpressing, tamoxifen-resistant breast cancer cells. Cancer Res. 60:5887-5894.
150. C. L. Arteaga and J. Baselga (2003). Clinical trial design and end points for epidermal growth factor receptor-targeted therapies: Implications for drug development and practice. Clin. Cancer Res. 9:1579-1589.
151. S. R. Johnston, J. Head, S. Pancholi, S. Detre, L. A. Martin, I. E. Smith and M. Dowsett (2003). Integration of signal transduction inhibitors with endocrine therapy: An approach to overcoming hormone resistance in breast cancer. Clin. Cancer Res. 9:524S-32S.
152. R. I. Nicholson, I. R. Hutcheson, M. E. Harper, J. M. Knowlden, D. Barrow, R. A. McClelland, H. E. Jones, A. E. Wakeling, and J. M. Gee (2002). Modulation of epidermal growth factor receptor in endocrine-resistant, estrogen-receptor-positive breast cancer. Ann. N. Y. Acad. Sci. 963:104-115.