Expression of p16 induces transcriptional downregulation of the RB gene

Xianjun Fang, Xiaomei Jin, Hong Ji Xu, Lin Liu, Hong Qi Peng, David Hogg, Jack A. Roth, Yinhua Yu, Fengji Xu, Robert C. Bast, Gordon B. Mills

    Research output: Contribution to journalArticle

    73 Scopus citations

    Abstract

    The RB and p16(INK4A) tumor suppressor genes function in the same pathway of cell cycle control. Previous evidence indicates that the p16(INK4A) gene is transcriptionally repressed by the RB gene product, pRB. In this study using human ovarian cancer cell lines, we found that RB protein and mRNA were expressed at higher levels in cell lines lacking p16 than in those with normal p16. Since this suggests a potential role of p16 in regulating the cellular level of pRB, we studied the effect of wild-type p16(INK4A) on expression of the RB gene. Introduction of p16(INK4A), carried by an adenovirus vector, into p16-negative cell lines dramatically decreased expression of RB protein and mRNA. Nuclei run-off assays demonstrated that p16 expression induced transcriptional downregulation of the RB gene. These results indicate that expression of RB is inversely regulated by p16. The findings reveal a new dimension of pRB-pl6 interaction and should have implications for p16(INK4A)-mediated gene therapy.

    Original languageEnglish (US)
    Pages (from-to)1-8
    Number of pages8
    JournalOncogene
    Volume16
    Issue number1
    DOIs
    StatePublished - Jan 8 1998

    Keywords

    • Expression
    • Ovarian cancer
    • RB
    • p16

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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  • Cite this

    Fang, X., Jin, X., Xu, H. J., Liu, L., Peng, H. Q., Hogg, D., Roth, J. A., Yu, Y., Xu, F., Bast, R. C., & Mills, G. B. (1998). Expression of p16 induces transcriptional downregulation of the RB gene. Oncogene, 16(1), 1-8. https://doi.org/10.1038/sj.onc.1201525