Skip NavigationSkip to Content
Return Return to Search Results

The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis

  1. Author:
    Dreijerink, K.
    Braga, E.
    Kuzmin, I.
    Geil, L.
    Duh, F. M.
    Angeloni, D.
    Zbar, B.
    Lerman, M. I.
    Stanbridge, E. J.
    Minna, J. D.
    Protopopov, A.
    Li, J. F.
    Kashuba, V.
    Klein, G.
    Zabarovsky, E. R.

  2. Author Address

    NCI, Intramural Res Support Program, Sci Applicat Int Corp, Bldg 560, Room 12-71, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Immunobiol Lab, Sci Applicat Int Corp, Frederick, MD 21702 USA. Karolinska Inst, Microbiol & Tumor Biol Ctr, S-17177 Stockholm, Sweden. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. Karolinska Inst, Ctr Genom Res, S-17177 Stockholm, Sweden. Kuzmin I NCI, Intramural Res Support Program, Sci Applicat Int Corp, Bldg 560, Room 12-71, Frederick, MD 21702 USA.
    1. Year: 2001
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 98
    2. 13
    3. Pages: 7504-7509
  4. Type of Article: Article
  1. Abstract:

    Clear cell-type renal cell carcinomas (clear RCC) are characterized almost universally by loss of heterozygosity on chromosome 30, which usually involves any combination of three regions: 3p25-p26 (harboring the VHL gene), 3p12-p14.2 (containing the FHIT gene), and 3p21-p22, implying inactivation of the resident tumor-suppressor genes (TSGs). For the 3p21-p22 region, the affected TSGs remain, at present, unknown. Recently, the RAS association family 1 gene (isoform RASSF1A), located at 3p21.3, has been identified as a candidate lung and breast TSC. In this report, we demonstrate aberrant silencing by hypermethylation of RASSF1A in both VHL-caused clear RCC tumors and clear RCC without VHL inactivation. We found hypermethylation of RASSF1A's CC-rich putative promoter region in most of analyzed samples, including 39 of 43 primary tumors (91%). The promoter was methylated partially or completely in all 18 RCC cell lines analyzed. Methylation of the CC-rich putative RASSF1A promoter region and loss of transcription of the corresponding mRNA were related causally. RASSF1A expression was reactivated after treatment with 5-aza-2 ' - deoxycytidine. Forced expression of RASSF1A transcripts in KRC/Y, a renal carcinoma cell line containing a normal and expressed VHL gene, suppressed growth on plastic dishes and anchorage-independent colony formation in soft agar. Mutant RASSF1A had reduced growth suppression activity significantly. These data suggest that RASSF1A is the candidate renal TSG gene for the 3p21.3 region.

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel