The biology and clinical relevance of the PTEN tumor suppressor pathway

Journal of Clinical Oncology

Volumn 22, Issue 14, 2004, Pages 2954-2963

  Sansal, Isabelle ^a   Sellers, William R ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PHOSPHATIDYLINOSITIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; RAPAMYCIN; RAPAMYCIN DERIVATIVE; ANTINEOPLASTIC AGENT; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATASE; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; PTEN PROTEIN, HUMAN; TUMOR SUPPRESSOR PROTEIN;

ARTICLE; BREAST CANCER; CANCER CELL; CANCER GENETICS; CANCER INCIDENCE; CANCER SUSCEPTIBILITY; COWDEN SYNDROME; ENDOMETRIUM CANCER; ENZYME ACTIVITY; FAMILIAL CANCER; GENE MUTATION; GENE TARGETING; GLIOBLASTOMA; HOMEOSTASIS; HUMAN; PRIORITY JOURNAL; PROSTATE CANCER; SIGNAL TRANSDUCTION; SOMATIC MUTATION; THYROID CANCER; TUMOR SUPPRESSOR GENE; CELL TRANSFORMATION; GENETIC PREDISPOSITION; GENETICS; MUTATION; NEOPLASM; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANTINEOPLASTIC AGENTS; CELL TRANSFORMATION, NEOPLASTIC; GENES, TUMOR SUPPRESSOR; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MUTATION; NEOPLASMS; PHOSPHORIC MONOESTER HYDROLASES; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; PTEN PHOSPHOHYDROLASE; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS;

EID: 4344602002     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/JCO.2004.02.141     Document Type: Article

References (100)

1. Li J, Yen C, Liaw D, et al: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275:1943-1947, 1997
2. Li DM, Sun H: TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res 57:2124-2129, 1997
3. Steck PA, Pershouse MA, Jasser SA, et al: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15:356-362, 1997
4. Eng C: Will the real Cowden syndrome please stand up: Revised diagnostic criteria. J Med Genet 37:828-830, 2000
5. Gorlin RJ, Cohen MM Jr, Condon LM, et al: Bannayan-Riley-Ruvalcaba syndrome. Am J Med Genet 44:307-314, 1992
6. Helen MR, Padberg GW, Peeters EA, et al: Localization of the gene for Cowden disease to chromosome 10q22-23. Nat Genet 13:114-116, 1996
7. Liaw D, Marsh DJ, Li J, et al: Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 16:64-67, 1997
8. Nelen MR, van Staveren WC, Peeters EA, et al: Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet 6:1383-1387, 1997
9. Marsh DJ, Dahia PL, Zheng Z, et al: Germline mutations in PTEN are present in Bannayan-Zonana syndrome. Nat Genet 16:333-334, 1997
10. Lynch ED, Ostermeyer EA, Lee MK, et al: Inherited mutations in PTEN that are associated with breast cancer, cowden disease, and juvenile polyposis. Am J Hum Genet 61:1254-1260, 1997
11. Liu W, James CD, Frederick L, et al: PTEN/MMAC1 mutations and EGFR amplification in glioblastomas. Cancer Res 57:5254-5257, 1997
12. Rasheed BK, Stenzel TT, McLendon RE, et al: PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 57:4187-4190, 1997
13. Wang SI, Pue J, Li J, et al: Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res 57:4183-4186, 1997
14. Chiariello E, Roz L, Albarosa R, et al: PTEN/MMAC1 mutations in primary glioblastomas and short-term cultures of malignant gliomas. Oncogene 16:541-545, 1998
15. Duerr EM, Rollbrocker B, Hayashi Y, et al: PTEN mutations in gliomas and glioneuronal tumors. Oncogene 16:2259-2264, 1998
16. Smith JS, Tachibana I, Passe SM, et al: PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 93:1246-1256, 2001
17. Podsypanina K, Ellenson LH, Nemes A, et al: Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc Natl Acad Sci U S A 96:1563-1568, 1999
18. Stambolic V, Tsao MS, Macpherson D, et al: High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/- mice. Cancer Res 60:3605-3611, 2000
19. Risinger JI, Hayes AK, Berchuck A, et al: PTEN/MMAC1 mutations in endometrial cancers. Cancer Res 57:4736-4738, 1997
20. Tashiro H, Blazes MS, Wu R, et al: Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 57:3935-3940, 1997
21. Lin WM, Forgacs E, Warshal DP, et al: Loss of heterozygosity and mutational analysis of the PTEN/MMAC1 gene in synchronous endometrial and ovarian carcinomas. Clin Cancer Res 4:2577-2583, 1998
22. Maxwell GL, Risinger JI, Gumbs C, et al: Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias. Cancer Res 58:2500-2503, 1998
23. Mutter GL, Lin MC, Fitzgerald JT, et al: Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 92:924-930, 2000
24. Risinger JI, Hayes K, Maxwell GL, et al: PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res 4:3005-3010, 1998
25. Sellers WR, Sawyers CA: Somatic genetics of prostate cancer: Oncogenes and tumor suppressors, in Kantoff PW (ed): Prostate Cancer Principles and Practice. Philadelphia, PA, Lippincott Williams & Wilkins, 2002
26. Wang SI, Parsons R, Ittmann M: Homozygous deletion of the PTEN tumor suppressor gene in a subset of prostate adenocarcinomas. Clin Cancer Res 4:811-815, 1998
27. Vlietstra RJ, van Alewijk DC, Hermans KG, et al: Frequent inactivation of PTEN in prostate cancer cell lines and xenografts. Cancer Res 58:2720-2723, 1998
28. Pesche S, Latil A, Muzeau F, et al: PTEN/MMAC1/TEP1 involvement in primary prostate cancers. Oncogene 16:2879-2883, 1998
29. Feilotter HE, Nagai MA, Boag AH, et al: Analysis of PTEN and the 10q23 region in primary prostate carcinomas. Oncogene 16:1743-1748, 1998
30. Dong JT, Sipe TW, Hyytinen ER, et al: PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate. Oncogene 17:1979-1982, 1998
31. Cairns P, Okami K, Halachmi S, et al: Frequent inactivation of PTEN/MMAC1 in primary prostate cancer. Cancer Res 57:4997-5000, 1997
32. Whang YE, Wu X, Suzuki H, et al: Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. Proc Natl Acad Sci U S A 95:5246-5250, 1998
33. Suzuki H, Freije D, Nusskern DR, et al: Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues. Cancer Res 58:204-209, 1998
34. McMenamin ME, Soung P, Perera S, et al: Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res 59:4291-4296, 1999
35. Guldberg P, thor Straten P, Birck A, et al: Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. Cancer Res 57:3660-3663, 1997
36. Tsao H, Zhang X, Benoit E, et al: Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines. Oncogene 16:3397-3402, 1998
37. Birck A, Ahrenkiel V, Zeuthen J, et al: Mutation and allelic loss of the PTEN/MMAC1 gene in primary and metastatic melanoma biopsies. J Invest Dermatol 114:277-280, 2000
38. Celebi JT, Shendrik I, Silvers DN, et al: Identification of PTEN mutations in metastatic melanoma specimens. J Med Genet 37:653-657, 2000
39. Reifenberger J, Wolter M, Bostrom J, et al: Allelic losses on chromosome arm 10q and mutation of the PTEN (MMAC1) tumour suppressor gene in primary and metastatic malignant melanomas. Virchows Arch 436:487-493, 2000
40. Pollock PM, Walker GJ, Glendening JM, et al: PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines. Melanoma Res 12:565-575, 2002
41. Kim SK, Su LK, Oh Y, et al: Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines. Oncogene 16:89-93, 1998
42. Kohno T, Takahashi M, Manda R, et al: Inactivation of the PTEN/MMAC1/TEP1 gene in human lung cancers. Genes Chromosomes Cancer 22:152-156, 1998
43. Yokomizo A, Tindall DJ, Drabkin H, et al: PTEN/MMAC1 mutations identified in small cell, but not in non-small cell lung cancers. Oncogene 17:475-479, 1998
44. Gronbaek K, Zeuthen J, Guldberg P, et al: Alterations of the MMAC1/PTEN gene in lymphoid malignancies. Blood 91:4388-4390, 1998
45. Dahia PL, Marsh DJ, Zheng Z, et al: Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors. Cancer Res 57:4710-4713, 1997
46. Halachmi N, Halachmi S, Evron E, et al: Somatic mutations of the PTEN tumor suppressor gene in sporadic follicular thyroid tumors. Genes Chromosomes Cancer 23:239-243, 1998
47. Bruni P, Boccia A, Baldassarre G, et al: PTEN expression is reduced in a subset of sporadic thyroid carcinomas: Evidence that PTEN-growth suppressing activity in thyroid cancer cells mediated by p27kip1. Oncogene 19:3146-3155, 2000
48. Feilotter HE, Coulon V, McVeigh JL, et al: Analysis of the 10q23 chromosomal region and the PTEN gene in human sporadic breast carcinoma. Br J Cancer 79:718-723, 1999
49. Freihoff D, Kempe A, Beste B, et al: Exclusion of a major role for the PTEN tumour-suppressor gene in breast carcinomas. Br J Cancer 79:754-758, 1999
50. Obata K, Morland SJ, Watson RH, et al: Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res 58:2095-2097, 1998
51. Yokomizo A, Tindall DJ, Hartmann L, et al: Mutation analysis of the putative tumor suppressor PTEN/MMAC1 in human ovarian cancer. Int J Oncol 13:101-105, 1998
52. Ali IU, Schriml LM, Dean M: Mutational spectra of PTEN/MMAC1 gene: A tumor suppressor with lipid phosphatase activity. J Natl Cancer Inst 91:1922-1932, 1999
53. Depowski PL, Rosenthal SI, Ross JS: Loss of expression of the PTEN gene protein product is associated with poor outcome in breast cancer. Mod Pathol 14:672-676, 2001
54. Perren A, Weng LP, Boag AH, et al: Immunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breast. Am J Pathol 155:1253-1260, 1999
55. Kurose K, Zhou XP, Araki T, et al: Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am J Pathol 158:2097-2106, 2001
56. Ebert MP, Fei G, Schandl L, et al: Reduced PTEN expression in the pancreas overexpressing transforming growth factor-beta 1. Br J Cancer 86:257-262, 2002
57. Stambolic V, MacPherson D, Sas D, et al: Regulation of PTEN transcription by p53. Mol Cell 8:317-325, 2001
58. Vazquez F, Ramaswamy S, Nakamura N, et al: Phosphorylation of the PTEN tail regulates protein stability and function. Mol Cell Biol 20:5010-5018, 2000
59. Vazquez F, Grossman SR, Takahashi Y, et al: Phosphorylation of the PTEN tail acts as an inhibitory switch by preventing its recruitment into a protein complex. J Biol Chem 276:48627-48630, 2001
60. Torres J, Pulido R: The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J Biol Chem 276:993-998, 2001
61. Miller SJ, Lou DY, Seldin DC, et al: Direct identification of PTEN Phosphorylation sites. FEBS Lett 528:145-153, 2002
62. Myers MP, Stolarov JP, Eng C, et al: P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase. Proc Natl Acad Sci U S A 94:9052-9057, 1997
63. Maehama T, Dixon JE: The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273:13375-13378, 1998
64. Rameh LE, Cantley LC: The role of phosphoinositide 3-kinase lipid products in cell function. J Biol Chem 274:8347-8350, 1999
65. Whitman M, Kaplan DR, Schaffhausen B, et al: Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation. Nature 315:239-242, 1985
66. Coughlin SR, Escobedo JA, Williams LT: Role of phosphatidylinositol kinase in PDGF receptor signal transduction. Science 243:1191-1194, 1989
67. Auger KR, Serunian LA, Soltoff SP, et al: PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell 57:167-175, 1989
68. Datta SR, Brunst A, Greenberg ME: Cellular survival: A play in three Akts. Genes Dev 13:2905-2927, 1999
69. Testa JR, Bellacosa A: AKT plays a central role in tumorigenesis. Proc Natl Acad Sci U S A 98:10983-10985, 2001
70. Vazquez F, Sellers WR: The PTEN tumor suppressor protein: An antagonist of phosphoinositide 3-kinase signaling. Biochim Biophys Acta 1470:M21-35, 2000
71. Chang HW, Aoki M, Fruman D, et al: Transformation of chicken cells by the gene encoding the catalytic subunit of Pl 3-kinase. Science 276:1848-1850, 1997
72. Bellacosa A, Testa JR, Staal SP, et al: A retroviral oncogene, akt, encoding a serinethreonine kinase containing an SH2-like region. Science 254:274-277, 1991
73. Staal SP: Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A 84:5034-5037, 1987
74. Ma YY, Wei SJ, Lin YC, et al: PIK3CA as an oncogene in cervical cancer. Oncogene 19:2739-2744, 2000
75. Shayesteh L, Lu Y, Kuo WL, et al: PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 21:99-102, 1999
76. Woenckhaus J, Steger K, Werner E, et al: Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma. J Pathol 198:335-342, 2002
77. Hui AB, Lo KW, Teo PM, et al: Genome wide detection of oncogene amplifications in nasopharyngeal carcinoma by array based comparative genomic hybridization. Int J Oncol 20:467-473, 2002
78. Hui AB, Lo KW, Yin XL, et al: Detection of multiple gene amplifications in glioblastoma multiforme using array-based comparative genomic hybridization. Lab Invest 81:717-723, 2001
79. Philp AJ, Campbell IG, Leet C, et al: The phosphatidylinositol 3′-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer Res 61:7426-7429, 2001
80. Jucker M, Sudel K, Horn S, et al: Expression of a mutated form of the p85alpha regulatory subunit of phosphatidylinositol 3-kinase in a Hodgkin's lymphoma-derived cell line (CO). Leukemia 16:894-901, 2002
81. Bellacosa A, de Feo D, Godwin AK, et al: Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer 64:280-285, 1995
82. Miwa W, Yasuda J, Murakami Y, et al: Isolation of DNA sequences amplified at chromosome 19q13.1-q13.2 including the AKT2 locus in human pancreatic cancer. Biochem Biophys Res Commun 225:968-974, 1996
83. Cheng JQ, Ruggeri B, Klein WM, et al: Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci U S A 93:3636-3641, 1996
84. Ruggeri BA, Huang L, Wood M, et al: Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinonias. Mol Carcinog 21:81-86, 1998
85. Giovannucci E: Insulin-like growth factor-l and binding protein-3 and risk of cancer. Norm Res 51:34-41, 1999(suppl 3)
86. Burgering BM, Kops GJ: Cell cycle and death control: Long live Forkheads. Trends Biochem Sci 27:352-360, 2002
87. Cohen P, Alessi DR, Cross DA: PDK1, one of the missing links in insulin signal transduction? FEBS Lett 410:3-10, 1997
88. Gingras AC, Raught B, Sonenberg N: Regulation of translation initiation by FRAP/mTOR. Genes Dev 15:807-826, 2001
89. Simpson L, Parsons R: PTEN: Life as a tumor suppressor. Exp Cell Res 264:29-41, 2001
90. Stambolic V, Suzuki A, de la Pompa JL, et al: Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 95:29-39, 1998
91. Di Cristofano A, Kotsi P, Peng YF, et al: Impaired Fas response and autoimmunity in Pten+/- mice. Science 285:2122-2125, 1999
92. Brunet A, Bonni A, Zigmond MJ, et al: Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857-868, 1999
93. Dijkers PF, Medema RH, Pals C, et al: Forkhead transcription factor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27(KIP1). Mol Cell Biol 20:9138-9148, 2000
94. Datta SR, Dudek H, Tao X, et al: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91:231-241, 1997
95. Li L, Liu F, Salmonsen RA, et al: PTEN in neural precursor cells: Regulation of migration, apoptosis, and proliferation. Mol Cell Neurosci 20:21-29, 2002
96. Kotelevets L, van Hengel J, Bruyneel E, et al: The lipid phosphatase activity of PTEN is critical for stabilizing intercellular junctions and reverting invasiveness. J Cell Biol 155:1129-1135, 2001
97. Liliental J, Moon SY, Lesche R, et al: Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases. Curr Biol 10:401-404, 2000
98. Tamura M, Gu J, Matsumoto K, et al: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 280:1614-1617, 1998
99. Zundel W, Schindler C, Haas-Kogan D, et al: Loss of PTEN facilitates HIF-1-mediated gene expression. Genes Dev 14:391-396, 2000
100. Bohni R, Riesgo-Escovar J, Oldham S, et al: Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97:865-875, 1999