Strategies to circumvent SV40 oncoprotein expression in malignant pleural mesotheliomas

Although nearly 60% of mesotheliomas contain SV40 early region DNA sequence s, the role of T/t antigens in initiating and maintaining the transformed s tate of mesothelioma cells remains unclear. The majority of mesothelioma ce lls which contain SV40 early region sequences exhibit extremely low basal e xpression of SV40 oncoproteins; however T/t antigen expression can he induc ed under conditions of cellular stress. Abrogation of SV40 T/t expression b y antisense techniques induces apoptosis in part via restoration of p53 fun ction, and enhances chemosensitivity in SV40(+) MPM cells by mechanisms whi ch have not been fully elucidated. This review briefly summarizes our ongoi ng efforts to define the role of SV40 oncoproteins in modulating the malign ant phenotype of mesothelioma cells, and highlights strategies which may pr ove efficacious in vivo for circumventing SV40 T/t antigen expression in me sotheliomas.