Strategies to circumvent SV40 oncoprotein expression in malignant pleural mesotheliomas

Although nearly 60% of mesotheliomas contain SV40 early region DNA sequences, the role of T/t antigens in initiating and maintaining the transformed state of mesothelioma cells remains unclear. The majority of mesothelioma cells which contain SV40 early region sequences exhibit extremely low basal expression of SV40 oncoproteins; however, T/t antigen expression can be induced under conditions of cellular stress. Abrogation of SV40 T/t expression by antisense techniques induces apoptosis in part via restoration of p53 function, and enhances chemosensitivity in SV40 (+) MPM cells by mechanisms which have not been fully elucidated. This review briefly summarizes our ongoing efforts to define the role of SV40 oncoproteins in modulating the malignant phenotype of mesothelioma cells, and highlights strategies which may prove efficacious in vivo for circumventing SV40 T/t antigen expression in mesotheliomas.