Skip NavigationSkip to Content
Return Return to Search Results

Inactivation of the von Hippel-Lindau tumor suppressor leads to selective expression of a human endogenous retrovirus in kidney cancer

  1. Author:
    Cherkasova, E.
    Malinzak, E.
    Rao, S.
    Takahashi, Y.
    Senchenko, V. N.
    Kudryavtseva, A. V.
    Nickerson, M. L.
    Merino, M.
    Hong, J. A.
    Schrump, D. S.
    Srinivasan, R.
    Linehan, W. M.
    Tian, X.
    Lerman, M. I.
    Childs, R. W.

  2. Author Address

    [Cherkasova, E.; Malinzak, E.; Rao, S.; Takahashi, Y.; Lerman, M. I.; Childs, R. W.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Senchenko, V. N.; Kudryavtseva, A. V.] Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia. [Nickerson, M. L.] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. [Merino, M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Hong, J. A.; Schrump, D. S.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Srinivasan, R.; Linehan, W. M.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Tian, X.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.;Childs, RW (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA;childsr@mail.nih.gov
    1. Year: 2011
    2. Date: Nov
  2. Journal: Oncogene
    1. 30
    2. 47
    3. Pages: 4697-4706
  4. Type of Article: Article
  5. ISSN: 0950-9232
  1. Abstract:

    A human endogenous retrovirus type E (HERV-E) was recently found to be selectively expressed in most renal cell carcinomas (RCCs). Importantly, antigens derived from this provirus are immunogenic, stimulating cytotoxic T cells that kill RCC cells in vitro and in vivo. Here, we show HERV-E expression is restricted to the clear cell subtype of RCC (ccRCC) characterized by an inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene with subsequent stabilization of hypoxia-inducible transcription factors (HIFs)-1 alpha and -2 alpha. HERV-E expression in ccRCC linearly correlated with HIF-2 alpha levels and could be silenced in tumor cells by either transfection of normal VHL or small interfering RNA inhibition of HIF-2 alpha. Using chromatin immunoprecipitation, we demonstrated that HIF-2 alpha can serve as transcriptional factor for HERV-E by binding with HIF response element (HRE) localized in the proviral 5' long terminal repeat (LTR). Remarkably, the LTR was found to be hypomethylated only in HERV-E-expressing ccRCC while other tumors and normal tissues possessed a hypermethylated LTR preventing proviral expression. Taken altogether, these findings provide the first evidence that inactivation of a tumor suppressor gene can result in aberrant proviral expression in a human tumor and give insights needed for translational research aimed at boosting human immunity against antigenic components of this HERV-E. Oncogene (2011) 30, 4697-4706; doi:10.1038/onc.2011.179; published online 23 May 2011

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1038/onc.2011.179
  3. View record in Web of Science®
  4. WOS: 000298033700002

Library Notes

  1. Fiscal Year: FY2011-2012
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