Gadd45介导抑癌基因BRCA1诱导的G2/M期阻滞

目前已经肯定,抑癌基因BRCAl是细胞周期监测点调控的重要因子,但BRCAl在细胞周期阻滞中的作用机制尚不完全清楚。本研究的目的是探讨Gadd45在BRCAl诱导的细胞周期阻滞中所起的作用。

Gadd45 mediated G2/M cell cycle arrest induced by BRCA1

BACKGROUND &OBJECTIVE: It is considered that tumor suppressor gene BRCA1 is an important factor in the regulation of cell cycle checkpoint, but the molecular mechanism by which BRCA1 regulates cell cycle G2/M arrest is less known. The objective of this study was to investigate the effects of Gadd45 on the BRCA1 induced cell growth suppression. METHODS: BRCA1 induction of Gadd45 protein was analyzed using Western blot assay following cells transfection with BRCA1 expression vector and cell sorting. Activation of the Gadd45 promoter by BRCA1 was determined by CAT assay. Effect of antisense Gadd45 on the BRCA1 induced cell cycle G2 M arrest was examined by flow cytometry analysis. And the effects of antisense Gadd45 on BRCA1 mediated growth suppression in HeLa and HCT116 cell lines was determined by colony formation assay. RESULTS: Gadd45 protein was highly induced after expression of BRCA1. BRCA1 strongly activated the Gadd45 promoter. Antisense Gadd45 substantially abrogated BRCA1 activated cell cycle G2 M arrest and BRCA1 induced cell growth suppression on HeLa and HCT116 cell lines. CONCLUSION: Gadd45 is a BRCA1 regulated downstream gene and mediates the role of BRCA1 in the control of cell cycle G2/M arrest and growth suppression.