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The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells

  1. Author:
    Kuzmin, I.
    Gillespie, J. W.
    Protopopov, A.
    Geil, L.
    Dreijerink, K.
    Yang, Y. F.
    Vocke, C. D.
    Duh, F. M.
    Zabarovsky, E.
    Minna, J. D.
    Rhim, J. S.
    Emmert-Buck, M. R.
    Linehan, W. M.
    Lerman, M. I.

  2. Author Address

    SAIC Frederick Inc, NCI, Intramural Res Support Program, Bldg 560,Room 12-34, Frederick, MD 21702 USA SAIC Frederick Inc, NCI, Intramural Res Support Program, Frederick, MD 21702 USA NCI, Immunobiol Lab, Ft Detrick, MD 21702 USA NCI, Pathol Lab, Bethesda, MD 20892 USA NCI, Urol Oncol Branch, Bethesda, MD 20892 USA Karolinska Inst, MTC & CGR, S-17177 Stockholm, Sweden VA Engelhardt Mol Biol Inst, Moscow 117984, Russia Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Bethesda, MD 20814 USA Kuzmin I SAIC Frederick Inc, NCI, Intramural Res Support Program, Bldg 560,Room 12-34, Frederick, MD 21702 USA
    1. Year: 2002
  2. Journal: Cancer Research
    1. 62
    2. 12
    3. Pages: 3498-3502
  4. Type of Article: Article
  1. Abstract:

    We analyzed expression status of the recently identified tumor suppressor gene RASSF1A in primary prostate carcinomas and in prostate cell lines. We found complete methylation of the RASSF1A promoter in 63 % of primary microdissected prostate carcinomas (7 of 11 samples). The remaining 4 samples (37 %) were partially methylated, possibly because of contamination with normal cells. No promoter methylation was observed in matching normal prostate tissues. High levels of RASSF1A transcript and no methylation of RASSF1A promoter were found in explanted primary normal prostate epithelial and stromal cells. Complete silencing and methylation of RASSFIA promoter was observed in five widely used prostate carcinoma cell lines, which acquired the ability to grow in culture spontaneously, including LNCaP, PC-3, ND-1, DU-145, 22Rv1 and one primary prostate carcinoma immortalized by overexpression of the human telomerase catalytic subunit (RC-58T/hTERT). However, no silencing of RASSF1A was found in four other prostate carcinoma cell lines, which were adapted for cell culture after transformation with human papillomaviral DNA. Suppression of cell growth in vitro was demonstrated after the reintroduction of RASSF1A-expressing construct into LNCaP prostate carcinoma cells. Our data implicate the RASSF1A gene in human prostate tumorigenesis.

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