Phosporylation/cytoplasmic localization of p21Cip1/WAF1 is associated with HER2/neu overexpression and provides a novel combination predictor for poor prognosis in breast cancer patients

Clinical Cancer Research

Volumn 10, Issue 11, 2004, Pages 3815-3824

  Xia, Weiya ^a   Chen, Jin Shing ^a,b   Zhou, Xian ^a   Sun, Pei Rong ^c   Lee, Dung Fang ^a,d   Liao, Yong ^a   Zhou, Binhua P ^a   Hung, Mien Chie ^a,d  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b NATIONAL TAIWAN UNIVERSITY HOSPITAL   (Taiwan)

^c Shanghai E Breast Disease Hospital   (China)

^d UNIVERSITY OF TEXAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL MARKER; EPIDERMAL GROWTH FACTOR RECEPTOR 2; PROTEIN KINASE B; PROTEIN P21; THREONINE; TUMOR MARKER; CDKN1A PROTEIN, HUMAN; CELL CYCLE PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR 1A;

ADULT; ARTICLE; BREAST CANCER; CANCER CELL; CANCER MORTALITY; CANCER PATIENT; CANCER SURVIVAL; CELLULAR DISTRIBUTION; CYTOPLASM; FEMALE; GENE OVEREXPRESSION; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; ONCOGENE NEU; PRIORITY JOURNAL; PROGNOSIS; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; BIOSYNTHESIS; BREAST TUMOR; CELL LINE; CHEMISTRY; FLUORESCENCE IN SITU HYBRIDIZATION; IMMUNOBLOTTING; IMMUNOPRECIPITATION; LYMPH NODE METASTASIS; METABOLISM; MIDDLE AGED; MULTIVARIATE ANALYSIS; PHOSPHORYLATION; PROPORTIONAL HAZARDS MODEL; TIME;

ADULT; BREAST NEOPLASMS; CELL CYCLE PROTEINS; CELL LINE; CYCLIN-DEPENDENT KINASE INHIBITOR P21; CYTOPLASM; HUMANS; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; IN SITU HYBRIDIZATION, FLUORESCENCE; LYMPHATIC METASTASIS; MIDDLE AGED; MULTIVARIATE ANALYSIS; PHOSPHORYLATION; PROGNOSIS; PROPORTIONAL HAZARDS MODELS; RECEPTOR, ERBB-2; THREONINE; TIME FACTORS;

EID: 2542640227     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-03-0527     Document Type: Article

References (31)

1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science (Wash DC) 1987; 235:177-82.
2. Yu D, Hung MC. Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene 2000;19:6115-21.
3. Ahmed NN, Grimes HL, Bellacosa A, Chan TO, Tsichlis PN. Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc Natl Acad Sci USA 1997;94:3627-32.
4. Downward J. Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 1998;10:262-7.
5. Zhou BP, Hu MC, Miller SA, et al. HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-κB pathways. J Biol Chem 2000;275:8027-31.
6. Peso LD, Gonzalez-Garcia M, Page C, Herrera R, Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science (Wash DC) 1997;278:687-9.
7. Cardone MH, Roy N, Stennicke HR, et al. Regulation of cell death protease caspase-9 by phosphorylation. Science (Wash DC) 1998;282: 1318-21.
8. Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999;96:857-68.
9. Kops GJ, De Ruiter ND, De Vries-Smits AM, Powell DR, Bos JL, Burgering BM. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature (Lond) 1999;398:630-4.
10. Zhou BP, Liao Y, Xia W, Zou Y, Spohn B, Hung MC. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat Cell Biol 2001;3:973-82.
11. Mayo LD, Donner DB. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci USA 2001;98:11598-603.
12. CIP/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat Cell Biol 2001;3:245-52.
13. Perez-Tenorio G, Stal O, Southeast Sweden Breast Cancer Group. Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer 2002;86:540-5.
14. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 1993;75:805-16.
15. Yang Z-Y, Perkins ND, Ohno T, Nabel EG, Nabel GJ. The p21 cyclin-dependent kinase inhibitor suppresses tumorigenicity in vivo. Nat Med 1995;1:1052-6.
16. CIP/WAF1 in monocytic differentiation. EMBO J 1999;18:1223-34.
17. Orend G, Hunter T, Ruoslahti E. Cytoplasmic displacement of cyclin E-cdk2 inhibitors p21Cip1 and p27Kip1 in anchorage-independent cells. Oncogene 1998;16:2575-83.
18. Huang S, Shu L, Dilling MB, et al. Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1). Mol Cell 2003;11:1491-501.
19. Ruan S, Okcu MF, Pong RC, et al. Attenuation of WAF1/Cip1 expression by an antisense adenovirus expression vector sensitizes glioblastoma cells to apoptosis induced by chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin. Clin Cancer Res 1999;5:197-202.
20. Zhang W, Kornblau SM, Kobayashi T, Gambel A, Claxton D, Deisseroth AB. High levels of constitutive WAF1/Cip1 protein are associated with chemoresistance in acute myelogenous leukemia. Clin Cancer Res 1995;1:1051-7.
21. Cip1/WAF1, which inhibits p34Cdc2 kinase. Mol Cell 1998;2:581-91.
22. Michels JJ, Duigou F, Marnay J, et al. Flow cytometry and quantitative immunohistochemical study of cell cycle regulation proteins in invasive breast carcinoma: prognostic significance. Cancer (Phila) 2003; 97:1376-86.
23. Gohring UJ, Bersch A, Becker M, Neuhaus W, Schondorf T. p21(waf) correlates with DNA replication but not with prognosis in invasive breast cancer. J Clin Pathol 2001;54:866-70.
24. Pellikainen MJ, Pekola TT, Ropponen KM, et al. p21WAF1 expression in invasive breast cancer and its association with p53, AP-2, cell proliferation, and prognosis. J Clin Pathol 2003;56:214-20.
25. Winters ZE, Hunt NC, Bradburn MJ, et al. Subcellular localization of cyclin B, Cdc2 and p21(WAF1/CIP1) in breast cancer: association with prognosis. Eur J Cancer 2001;37:2405-12.
26. Porter AF. Protein translocation in apoptosis. Trends Cell Biol 1999;9:394-401.
27. Beahrs OH, Henson DE, Hutter RVP, Myers M, editors. American Joint Committee on Cancer: manual for staging of cancer, 3rd ed. Philadelphia: J. B. Lippincott, 1988.
28. Zou Y, Peng H, Zhou B, et al. Systemic tumor suppression by the proapoptotic gene bik. Cancer Res 2002;62:8-12.
29. Xia W, Lau Y-K, Zhang H-Z, et al. Strong correlation between c-erbB-2 overexpression and over all survival of patients with oral squamous cell carcinoma Clin Cancer Res 1997;3:3-9.
30. Li Y, Dowbenko D, Lasky LA. AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival. J Biol Chem 2002;277:11352-61.
31. Osborne CK, Bardou V, Hopp TA, et al. Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J Natl Cancer Inst (Bethesda) 2003;95:353-61.