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

Candace M. Howard, Pier Paolo Claudio, Gary L. Gallia, Jennifer Gordon, Giovan Giacomo Giordano, Walter W. Hauck, Kamel Khalili, Antonio Giordano

Research output: Contribution to journalArticlepeer-review

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)1451-1460
Number of pages10
JournalJournal of the National Cancer Institute
Volume90
Issue number19
DOIs
StatePublished - Oct 7 1998
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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