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 Mills

Research output: Contribution to journalArticle

72 Citations (Scopus)

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
StatePublished - Jan 8 1998
Externally publishedYes

Fingerprint

Cyclin-Dependent Kinase Inhibitor p16
Down-Regulation
Genes
Cell Line
p16 Genes
Messenger RNA
Cell Cycle Checkpoints
Tumor Suppressor Genes
Adenoviridae
Genetic Therapy
Ovarian Neoplasms
Proteins
Gene Expression

Keywords

  • Expression
  • Ovarian cancer
  • p16
  • RB

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Fang, X., Jin, X., Xu, H. J., Liu, L., Peng, H. Q., Hogg, D., ... Mills, G. (1998). Expression of p16 induces transcriptional downregulation of the RB gene. Oncogene, 16(1), 1-8.

Expression of p16 induces transcriptional downregulation of the RB gene. / Fang, Xianjun; Jin, Xiaomei; Xu, Hong Ji; Liu, Lin; Peng, Hong Qi; Hogg, David; Roth, Jack A.; Yu, Yinhua; Xu, Fengji; Bast, Robert C.; Mills, Gordon.

In: Oncogene, Vol. 16, No. 1, 08.01.1998, p. 1-8.

Research output: Contribution to journalArticle

Fang, X, Jin, X, Xu, HJ, Liu, L, Peng, HQ, Hogg, D, Roth, JA, Yu, Y, Xu, F, Bast, RC & Mills, G 1998, 'Expression of p16 induces transcriptional downregulation of the RB gene', Oncogene, vol. 16, no. 1, pp. 1-8.
Fang X, Jin X, Xu HJ, Liu L, Peng HQ, Hogg D et al. Expression of p16 induces transcriptional downregulation of the RB gene. Oncogene. 1998 Jan 8;16(1):1-8.
Fang, Xianjun ; Jin, Xiaomei ; Xu, Hong Ji ; Liu, Lin ; Peng, Hong Qi ; Hogg, David ; Roth, Jack A. ; Yu, Yinhua ; Xu, Fengji ; Bast, Robert C. ; Mills, Gordon. / Expression of p16 induces transcriptional downregulation of the RB gene. In: Oncogene. 1998 ; Vol. 16, No. 1. pp. 1-8.
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