VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells

Ranjit S. Bindra, Robert Stearman, James R. Vasselli, W. Marston Linehan, Richard D. Klausner

Research output: Contribution to journalArticle

103 Scopus citations


Renal cell carcinoma is associated with mutation of the yon von Hippel-Lindau (VHL) tumor suppressor gene. Cell lines derived from these tumors cannot exit the cell cycle when deprived of growth factors, and the ability to exit the cell cycle can be restored by the reintroduction of wild-type protein VHL (pVHL). Here, we report that cyclin D1 is over-expressed and remains inappropriately high in during contact inhibition in pVHL-deficient cell lines. In addition, hypoxia increased the expression of cyclin D1 specifically in pVHL-negative cell lines into which pVHL expression was restored. Hypoxic-induction of cyclin D1 was not observed in other pVHL-positive cell lines. This suggests a model whereby in some kidney cell types, pVHL may regulate a proliferative response to hypoxia, whereas the loss of pVHL leads to constitutively elevated cyclin D1 and abnormal proliferation under normal growth conditions.

Original languageEnglish (US)
Pages (from-to)3014-3019
Number of pages6
JournalCancer Research
Issue number11
StatePublished - Jun 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Bindra, R. S., Stearman, R., Vasselli, J. R., Linehan, W. M., & Klausner, R. D. (2002). VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells. Cancer Research, 62(11), 3014-3019.