The retinoblastoma protein (Rb) as an anti-apoptotic factor: expression of Rb is required for the antiapoptotic function of BAG-1 protein in colorectal tumour cells

被引:33
作者
Collard, T. J. [1 ]
Urban, B. C. [1 ]
Patsos, H. A. [1 ]
Hague, A. [2 ]
Townsend, P. A. [3 ]
Paraskeva, C. [1 ]
Williams, A. C. [1 ]
机构
[1] Univ Bristol, Canc Res UK Colorectal Tumour Biol Res Grp, Sch Cellular & Mol Med, Bristol BS8 1TD, Avon, England
[2] Univ Bristol, Sch Oral & Dent Sci, Bristol BS8 1TD, Avon, England
[3] Univ Southampton, Southampton Gen Hosp, Sch Med, Canc Sci Div, Southampton, Hants, England
来源
CELL DEATH & DISEASE | 2012年 / 3卷
基金
英国医学研究理事会; 英国惠康基金;
关键词
BAG-1; Rb; NF-kappa B; apoptosis; colorectal cancer; osteosarcoma; HUMAN COLONIC ADENOMA; P53; SURVIVAL; ISOFORMS; GENE; INHIBITION; INITIATION; INTERACTS; CANCERS; TARGET;
D O I
10.1038/cddis.2012.142
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Although the retinoblastoma-susceptibility gene RB1 is inactivated in a wide range of human tumours, in colorectal cancer, the retinoblastoma protein (Rb) function is often preserved and the RB locus even amplified. Importantly, we have previously shown that Rb interacts with the anti-apoptotic Bcl-2 associated athanogene 1 (BAG-1) protein, which is highly expressed in colorectal carcinogenesis. Here we show for the first time that Rb expression is critical for BAG-1 anti-apoptotic activity in colorectal tumour cells. We demonstrate that Rb expression not only increases the nuclear localisation of the anti-apoptotic BAG-1 protein, but that expression of Rb is required for inhibition of apoptosis by BAG-1 both in a gamma-irradiated Saos-2 osteosarcoma cell line and colorectal adenoma and carcinoma cell lines. Further, consistent with the fact that nuclear BAG-1 has previously been shown to promote cell survival through increasing nuclear factor (NF)-kappa B activity, we demonstrate that the ability of BAG-1 to promote NF-kappa B activity is significantly inhibited by repression of Rb expression. Taken together, data presented suggest a novel function for Rb, promoting cell survival through regulating the function of BAG-1. As BAG-1 is highly expressed in the majority of colorectal tumours, targeting the Rb-BAG-1 complex to promote apoptosis has exciting potential for future therapeutic development. Cell Death and Disease (2012) 3, e408; doi:10.1038/cddis.2012.142; published online 11 October 2012
引用
收藏
页码:e408 / e408
页数:9
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