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Is annexin 7 a tumor suppressor gene in prostate cancer?

The Pharmacogenomics Journal volume 1, pages 92–94 (2001)Cite this article

Two features make the prostate and its tumors unusual. First, the prostate gland continues to grow throughout adult life, even doubling in size between the second and fourth decades.1 As a result, benign prostate hypertrophy affects most aging men to some degree. Second, and much more serious, cancer of the prostate is the most frequent malignant tumor and second leading cause of cancer-related deaths among men in the United States and Europe.2 While one out of every 11 men will develop prostate cancer during their lifetime, many tumors remain clinically quiescent. Without entirely reliable ways of predicting which tumors will progress, many prostate cancer patients are treated aggressively with radical prostatectomy or radiation therapy on the chance of cure, but often at the price of devastating treatment side-effects such as urinary incontinence and sexual impotence. Thus, there is a clear need for markers of cellular growth potential as new diagnostic and therapeutic targets in prostate cancer.

In 1971, Knudson postulated that tumors arise from as few as two stochastic events;3 this empirically based hypothesis—known as the ‘two-hit’ model—has been supported by using molecular genetic approaches. A major tool for these studies has been the determination of loss of heterozygosity (LOH) in tumors, which is a refined version of cytogenetic analysis that can sensitively detect genetic alterations and infer subtle chromosomal mechanisms. The method can be used in sporadic tumor types because shared regions of LOH are likely to reflect potential sites for tumor suppressor genes and common mechanisms for tumorigenesis. It is now widely accepted that human tumors originate and undergo malignant progression through a multi-step process in which growth-advantageous genetic events accumulate.2,4,5,6 Inactivation of tumor suppressor genes is a critical step in the development of human cancer. Gene inactivation is frequently accompanied by the loss of the chromosome or chromosomal region in which the tumor suppressor resides. This hypothesis was developed by using retinoblastoma as a model7 and has subsequently been tested in a large variety of tumors, perhaps most rigorously in human colorectal cancer5 and malignant gliomas.6

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References

  1. Folkman J . Is tissue mass regulated by vascular endothelial cells? Prostate as the first evidence Endocrinology 1998 139: 441–442

    Article  CAS  PubMed  Google Scholar 

  2. DeVita VT Jr, Hellman S, Rosenberg SA . Cancer. Principles and Practice of Oncology, 5th edition Lippincott-Raven Publishers 1997

  3. Knudson AG . Mutation and cancer: statistical study of retinoblastoma Proc Natl Acad Sci USA 1971 68: 820–823

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lasko D, Cavenee W, Nordenskjold M . Loss of constitutional heterozygosity in human cancer Annu Rev Genet 1991 25: 281–314

    Article  CAS  PubMed  Google Scholar 

  5. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M et al . Genetic alterations during colorectal-tumor development N Engl J Med 1988 319: 525–532

    Article  CAS  PubMed  Google Scholar 

  6. Nagane M, Huang HJ, Cavenee WK . Advances in the molecular genetics of gliomas Curr Opin Oncol 1997 9: 215–222

    Article  CAS  PubMed  Google Scholar 

  7. Cavenee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL et al . Expression of recessive alleles by chromosomal mechanisms in retinoblastoma Nature 1983 305: 779–784

    Article  CAS  PubMed  Google Scholar 

  8. Navone NM, Troncoso P, Pisters LL, Goodrow TL, Palmer JL, Nichols WW et al . p53 protein accumulation and gene mutation in the progression of human prostate carcinoma J Natl Cancer Inst 1993 85: 1657–1669

    Article  CAS  PubMed  Google Scholar 

  9. McMenamin ME, Soung P, Perera S, Kaplan I, Loda M, Sellers WR . Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage Cancer Res 1999 59: 4291–4296

    CAS  PubMed  Google Scholar 

  10. Halvorsen OJ, Hostmark J, Haukaas S, Hoisaeter PA, Akslen LA . Prognostic significance of p16 and CDK4 proteins in localized prostate carcinoma Cancer 2000 82: 416–424

    Article  Google Scholar 

  11. Verma RS, Manikal M, Conte RA, Godec CJ . Chromosomal basis of adenocarcinoma of the prostate Cancer Invest 1999 17: 441–447

    Article  CAS  PubMed  Google Scholar 

  12. Ueda T, Ichikawa T, Tamaru J, Mikata A, Akakura K, Akimoto et al. Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer Am J Pathol 1996; 149 1435–1440

    Google Scholar 

  13. Paul R, Ewing CM, Jarrard DF, Isaacs WB . The cadherin cell-cell adhesion pathway in prostate cancer progression Br J Urol 1997 79: 37–43

    Article  PubMed  Google Scholar 

  14. Cher ML, Bova GS, Moore DH, Small EJ, Carroll PR, Pin SS et al . Genetic alterations in untreated metastases and androgen-independent prostate cancer detected by comparative genomic hybridization and allelotyping Cancer Res 1996 56: 3091–3102

    CAS  PubMed  Google Scholar 

  15. Trybus TM, Burgess AC, Wojno KJ, Glover TW, Macoska JA . Distinct areas of allelic loss on chromosomal regions 10p and 10q in human prostate cancer Cancer Res 1996 56: 2263–2267

    CAS  PubMed  Google Scholar 

  16. Raynal P, Pollard HB . Annexins: the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins Biochem Biophys Acta 1994 1197: 63–93

    CAS  PubMed  Google Scholar 

  17. Bastian BC . Annexins in cancer and autoimmune diseases Cell Mol Life Sci 1997 53: 554–556

    Article  CAS  PubMed  Google Scholar 

  18. Shirvan A, Srivastava M, Wang MG, Cultraro C, Magendzo K, McBride OW et al . Divergent structure of the human synexin (annexin VII) gene and assignment to chromosome 10 Biochemistry 1994 33: 6888–6901

    Article  CAS  PubMed  Google Scholar 

  19. Kuijpers GAJ, Lee G, Pollard HB . Immunolocalization of synexin (annexin VII) in adrenal chromaffin granules and chromaffin cells: evidence for a dynamic role in the secretory process Cell Tissue Res 1992 269: 323–330

    Article  CAS  PubMed  Google Scholar 

  20. Doring V, Schleicher M, Noegel AA . Dictyostelium annexin VII (synexin). cDNA sequence and isolation of a gene disruption mutant J Biol Chem 1991 266: 17509–17515

    CAS  PubMed  Google Scholar 

  21. Srivastava M, Atwater I, Glasman M, Leighton X, Goping G, Caohuy H et al . Defects in inositol 1,4,5-trisphosphate receptor expression, Ca(2+) signaling, and insulin secretion in the anx7 (+/−) knockout mouse Proc Natl Acad Sci USA 1999 96: 13783–13788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hansen MF, Cavenee WK . Tumor suppressors: recessive mutations that lead to cancer Cell 1988 53: 173–174

    Article  CAS  PubMed  Google Scholar 

  23. Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC et al . 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers Nature Med 1995 1: 682–692

    Article  Google Scholar 

  24. Srivastava M, Bubendorf L, Srikantan V, Fossom L, Nolan L, Glasman M et al . ANX7, a candidate tumor suppressor gene for prostate Proc Natl Acad Sci USA 2001 98: 4575–4580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Cardó-Vila, R Pasqualini & W Arap

  2. Ludwig Institute for Cancer Research—San Diego Branch, La Jolla, CA, USA

    K C Arden & W K Cavenee

Authors
  1. M Cardó-Vila
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  2. K C Arden
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  3. W K Cavenee
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  4. R Pasqualini
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  5. W Arap
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Correspondence to R Pasqualini or W Arap.

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Cardó-Vila, M., Arden, K., Cavenee, W. et al. Is annexin 7 a tumor suppressor gene in prostate cancer?. Pharmacogenomics J 1, 92–94 (2001). https://doi.org/10.1038/sj.tpj.6500028

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