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
Department of Molecular Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, USA.
Oncogene. 1998 Jan 8;16(1):1-8. doi: 10.1038/sj.onc.1201525.
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-p16 interaction and should have implications for p16(INK4A)-mediated gene therapy.
RB和p16(INK4A)肿瘤抑制基因在细胞周期调控的同一途径中发挥作用。先前的证据表明，p16(INK4A)基因受到RB基因产物pRB的转录抑制。在这项使用人卵巢癌细胞系的研究中，我们发现，与p16正常的细胞系相比，缺乏p16的细胞系中RB蛋白和mRNA的表达水平更高。由于这表明p16在调节pRB细胞水平方面具有潜在作用，我们研究了野生型p16(INK4A)对RB基因表达的影响。通过腺病毒载体将p16(INK4A)导入p16阴性细胞系后，RB蛋白和mRNA的表达显著降低。细胞核径流试验表明，p16表达诱导RB基因的转录下调。这些结果表明，RB的表达受到p16的反向调节。这些发现揭示了pRB - p16相互作用的一个新层面，并且应该对p16(INK4A)介导的基因治疗具有启示意义。
