The American Journal of Surgery
Volume 195, Issue 6 , Pages 719-725 , June 2008

Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence?

  • Tamer Colakoglu, M.D.

      Affiliations

    • Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
    • Corresponding Author InformationCorresponding author. Tel.: +90-322-327 27 27; fax: +90-322-327 12 76.
    • ,
  • Sedat Yildirim, M.D.

      Affiliations

    • Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
    • ,
  • Fazilet Kayaselcuk, M.D.

      Affiliations

    • Faculty of Medicine, Department of Pathology, Baskent University, Ankara, Turkey
    • ,
  • Tarik Zafer Nursal, M.D.

      Affiliations

    • Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
    • ,
  • Ali Ezer, M.D.

      Affiliations

    • Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
    • ,
  • Turgut Noyan, M.D.

      Affiliations

    • Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
    • ,
  • Hamdi Karakayali, M.D.

      Affiliations

    • Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey
    • ,
  • Mehmet Haberal, M.D.

      Affiliations

    • Faculty of Medicine, Department of General Surgery, Baskent University, Ankara, Turkey

Received 13 March 2007 ,Revised 28 May 2007

References 

  1. Steck PA, Pershose MA, Jasser SA, et al. Identification of a candidate tumor suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997;15:356–362
  2. Cantley LC, Neel BG. New insights into tumor suppression; PTEN suppresses tumor formation by restraining phosphoinositide 3-kinase/Akt pathway. Proc Natl Acad Sci U S A. 1999;96:4240–4245
  3. Wu X, Senechal K, Neshat MS, et al. The PTEN/MMAC1 tumor suppressor phosphatase fuctions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway. Proc Natl Acad Sci U S A. 1998;95:15587–15591
  4. Auger KR, Serunian LA, Soltoff SP, et al. PDGF-dependent tyrosine phosphorylation stimulates production of novel polyphosphoinositides in intact cells. Cell. 1989;57:167–175
  5. Downward J. Ras signalling and apoptosis. Curr Opin Genet Dev. 1998;8:49–54
  6. Ahmed NN, Grimes HL, Bellacosa A, et al. Transduction of IL-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc Natl Acad Sci U S A. 1997;94:3627–3632
  7. Myers MP, Pass I, Batty IH, et al. The lipid phosphatase activity of PTEN is critical for its tumor suppression. Proc Natl Acad Sci U S A. 1998;95:13513–13518
  8. Suzuki J, de la Pompa JL, Stambolic V, et al. High cancer susceptility and embryonic lethality associated with mutation of PTEN tumor suppressor gene in mice. Curr Biol. 1998;8:1169–1178
  9. Datta K, Franke TF, Chan TO, et al. AH/AP domain mediated interaction between AKT molecules and its potential role in AKT regulation. Moll Cell Biol. 1995;15:2304–2310
  10. Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell. 1999;98:857–868
  11. Zhou H, Li X-M, Meinkoth J, et al. Akt regulates cell survival and apoptosis at a postmitchondrial level. J Cell Biol. 2000;151:483–494
  12. Cross DA, Alessi DA, Cohen P, et al. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995;378:785–789
  13. Diehl JA, Cheng M, Roussel MF, et al. Glycogen synthase kinase 3 beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 1998;12:3499–3511
  14. deGraffenried LA, Fulcher L, Friedrichs WE, et al. Reduced PTEN expression in breast cancer cells confers susceptibility to inhibitors of the PI3 kinase/Akt pathway. Ann Oncol. 2004;15:1510–1516
  15. Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev. 1999;13:2905–2927
  16. Nam SY, Lee HS, Jung G, et al. Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis. APMIS. 2003;111:1105–1
  17. Oki E, Baba H, Tokunaga E, et al. Akt phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancer. Int J Cancer. 2005;117:376–380
  18. Panigrahi AR, Pinder SE, Chan SY, et al. The role of PTEN and its signalling pathways, including Akt, in breast cancer; an assessment of relationships with other prognostic factors and with outcome. J Pathol. 2004;204:93–100
  19. Chung MJ, Jung SH, Lee BJ, et al. Inactivation of PTEN gene protein product is associated with invasiveness and metastasis, but not angiogenesis, of breast cancer. Pathol Int. 2004;54:10–15
  20. Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol. 2004;22:2954–2963
  21. David O. Akt and PTEN: new diagnostic markers of non-small cell lung cancer?. J Cell Mol Med. 2001;5:430–433
  22. Roy HK, Olusola BF, Clemens DL, et al. Akt proto- oncogene overexpression is an early event during sporadic colon carcinogenesis. Carcinogenesis. 2002;23:201–205
  23. Sheng H, Shao J, Townsend CM, et al. Phosphatidylinositol 3-kinase mediates proliferative signals in intestinal epithelial cells. Gut. 2003;52:1472–1478
  24. Khaleghpour K, Li Y, Banville D, et al. Involvement of PI-3 kinase signaling pathway in progression of colon adenocarcinoma. Carcinogenesis. 2004;25:241–248
  25. Guanti G, Resta N, Simone C, et al. Involvement of PTEN mutations in the genetic pathways of colorectal carcinogenesis. Hum Mol Genet. 2000;9:283–287
  26. Zhou XP, Loukola A, Salovaara R, et al. PTEN mutational spectra, expression levels, and subcellular localization in microsatellite stable and unstable colorectal cancers. Am J Pathol. 2002;161:439–447
  27. Molatore S, Ranzani GN. Genetics of colorectal polyps. Tec Coloproctol. 2004;8:240–242
  28. Jass JR, Baker K, Zlobec I, et al. Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a ‘fusion’ pathway to colorectal cancer. Histopathology. 2006;49:121–131
  29. Chi SG, Kim HJ, Park BJ, et al. Mutational abrogation of the PTEN/MMAC1 gene in gastrointestinal polyps in patients with Cowden disease. Gastroenterology. 1998;115:1084–1089
  30. Eng C. Constipation, polyps, or cancer? (Let PTEN predict your future). Am J Med Genet A. 2003;122:315–322
  31. Salvesen HB, Stefansson I, Kretzschmar EI, et al. Significance of PTEN alterations in endometrial carcinoma: a population–based study of mutations, promoter methylation and PTEN protein expression. Int J Oncol. 2004;25:1615–1623
  32. Chen WC, Lin MS, Zhang BF, et al. Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray. World J Gastroenterol. 2007;13:699–708
  33. Rychahou PG, Jackson NL, Silva SR, et al. Targeted molecular therapy of the PI3K pathway (Therapeutic significance of PI3K subunit targeting in colorectal carcinoma). Ann Surg. 2006;243:833–844
  34. Lindblom A. Different mechanisms in the tumorigenesis of proximal and distal colon cancers. Curr Opin Oncol. 2001;13:63–69
  35. Schondorf T, Dostal A, Grabmann J, et al. Single mutations of PTEN gene in recurrent ovarian carcinomas. J Soc Gynecol Investig. 2000;7:313–316
  36. Tang JM, He Qy, Guo RX, et al. Phosphorylated Akt overexpression and loss of PTEN expression in non-small lung cancer confers poor prognosis. Lung Cancer. 2006;51:181–191
  37. McMenamin ME, Soung P, Perera S, et al. Loss of PTEN expression paraffin-embedded primary prostate cancer with high Gleason score and advancad stage. Cancer Res. 1999;59:4291–4296
  38. Saal LH, Holm K, Maurer M, et al. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res. 2005;65:2554–2559
  39. Shi W, Zhang X, Pintilie M, et al. Dysregulated PTEN-PKB and negative receptor status in human breast cancer. Int J Cancer. 2003;104:195–203
  40. Hara S, Oya M, Mizuno R, et al. Akt activation in renal cell carcinoma: contribution of a decreased expression and the induction of apoptosis by Akt inhibitor. Ann Oncol. 2005;16:928–933
  41. Stiles B, Gilman V, Khanzenzon N, et al. Essential role of akt-1/protein kinase B in PTEN-cotrolled tumorigenesis. Moll Cell Biol. 2002;22:3842–3851
  42. Osaki M, Oshimura M, Ito H, et al. PI3K-Akt pathway: its fuctions and alterations in human cancer. Apoptosis. 2004;9:667–676
  43. Phillips WA, St Clair F, Munday AD, et al. Increased levels of phosphatidylinositil 3-kinase activity. Cancer. 1998;83:41–47
  44. Itoh N, Semba S, Ito M, et al. Phosphorylation of Akt/PKB is required for suppression of cancer apoptosis and tumor progression in human colorectal carcinoma. Cancer. 2002;94:3127–3134
  45. Woolfson K. Tumor markers in cancer of colon and rectum. Dis Colon Rectum. 1991;34:506–511

PII: S0002-9610(08)00176-1

doi: 10.1016/j.amjsurg.2007.05.061

The American Journal of Surgery
Volume 195, Issue 6 , Pages 719-725 , June 2008

Article Tools

* Image Usage & Resolution