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J Natl Cancer Inst. 1998 Oct 7;90(19):1451-60.

Retinoblastoma-related protein pRb2/p130 and suppression of tumor growth in vivo.

Author information

1
Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, and Sbarro Institute for Cancer Research and Molecular Medicine, Philadelphia, PA 19102, USA.

Abstract

BACKGROUND:

The RB/p105 and p107 genes of the retinoblastoma family are tumor suppressor genes whose proteins are inactivated by interaction with T-antigen proteins encoded by polyomaviruses (e.g., simian virus 40 and human JC virus), which have been found to be highly tumorigenic in animals. A variety of indirect evidence suggests that another member of the retinoblastoma gene family, RB2/p130, is also a tumor suppressor gene. To investigate the putative tumor suppressor activity of RB2/p130 more directly, we utilized a tetracycline-regulated gene expression system to control expression of the encoded protein pRb2/p130 in JC virus-induced hamster brain tumor cells and to study the effects of pRb2/p130 on the growth of such tumor cells in nude mice. The ability of pRb2/p130 to interact with JC virus T antigen was also studied.

METHODS:

Northern blot hybridization analyses were performed on samples of total cellular RNA to measure RB2/p130 and beta-actin messenger RNA levels. Immunoprecipitation and western blot analyses were used to determine T-antigen and pRb2/p130 protein levels and to assess the phosphorylation status of these proteins. Tumor cells were injected subcutaneously into nude mice, and tumor growth, with or without induced expression of pRb2/p130, was monitored.

RESULTS:

Induction of pRb2/p130 expression brought about a 3.2-fold, or 69% (95% confidence interval = 64%-73%), reduction in final tumor mass in nude mice. We also demonstrated that JC virus T antigen binds hypophosphorylated pRb2/p130 and that stimulation of pRb2/p130 expression overcomes cellular transformation mediated by this antigen.

CONCLUSION:

Our findings support the hypothesis that RB2/p130 is a tumor suppressor gene.

PMID:
9776410
DOI:
10.1093/jnci/90.19.1451
[Indexed for MEDLINE]

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