The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas

Abstract

The oncoprotein of simian virus-40, SV40 large T-antigen (Tag), is reported to target and to inactivate growth suppressive proteins such as the retinoblastoma family and p53 (ref. 4, 5), leading to transformation of human cell lines in vitro, tumor production in rodents, and detection of Tag in several human cancers including mesotheliomas. The retinoblastoma family contains three members, pRb, p107 and pRb2/p130 (ref. 9), that are phosphorylated in a cell cycle-dependent manner, have cell growth suppressive properties and bind to specific members of the E2F family and various cyclins. Even though mesotheliomas are among the most aggressive human cancers, alterations of important cell-cycle "controllers," such as the Rb family genes, have never been reported in these tumors. We found the presence of SV40-like sequences in 86% of 35 archival specimens of mesothelioma. We also demonstrated that SV40 Tag, isolated from frozen biopsies of human mesothelioma, binds each of the retinoblastoma family proteins, pRb, p107 and pRb2/p130, in four of four specimens. We propose that the tumorigenic potential of SV40 Tag in some human mesotheliomas may arise from its ability to interact with and thereby inactivate several tumor and/or growth suppressive proteins.

Simian virus 40, poliovaccines and human tumors: a review of recent developments

“…The ®nding of Tag-protein expression in some human mesotheliomas further decreased the possibility of PCR contamination. Several other laboratories have replicated our results in mesothelioma (Cristaudo et al, 1995;Pepper et al, 1996;De Luca et al, In press, Gri th and Weiss, 1997; Galateau-Salle, 1997; Mutti L, personal communication; Testa JR., personal communication). None of these laboratories had previously worked with SV40.…”

Association of SV40 with human tumors

“…When SV40 positive mesothelioma cell lines were treated with Tag antisense, the p53 pathway was restored, and p21 expression was resumed, which led to eventual growth arrest and apoptosis of these cells (Schrump and Waheed, 2001). Aside from p53, Tag was also shown to interact in a similar manner with the retinoblastoma tumor suppressor family pRb, p107 and pRB2/p130 (De Luca et al, 1997). Thus, Tag appears biologically active in human mesothelioma, suggesting that it may play a role in human mesothelioma development.…”

Latent membrane protein 1 suppresses RASSF1A expression, disrupts microtubule structures and induces chromosomal aberrations in human epithelial cells

“…The p53 and Rb tumor-suppressor genes are crucial in cell cycle regulation checkpoints and are common targets of inactivation by viral oncogenes, including large T antigen of SV40 virus (De Luca et al, 1997) and E6 and E7 of human papilloma virus (Balsitis et al, 2005). However, functional interactions of EBV oncogenes with tumor-suppressor genes during NPC development are unclear.…”