SV40 virus transformation down-regulates endothelin receptor

Abstract

Simian virus 40 (SV40) is an oncogenic DNA virus that induces malignant transformation. Endothelin (ET), a 21 amino acid peptide with mitogenic and anti-apoptotic effects, binds to G-protein coupled ET A and ET B receptors. This report examines the effect of SV40 transformation on the expression of ET receptors. Results from receptor binding and reverse transcription (RT)-polymerase chain reaction (PCR) studies show that human lung fibroblasts IMR90 and WI38 express both ET A and ET B receptors, and that the expression of both receptors is significantly down-regulated in IMR90-SV40 and WI38-SV40, cell lines derived from IMR90 and WI38 with SV40 virus transformation. Receptor binding and RT-PCR analysis of 3A(tPA-30-1), a cell line derived from human placenta that expresses a higher level of SV40 large T-antigen at the permissive temperature (33°C) than at the restrictive temperature (40°C), further demonstrates that there is an inverse correlation between the expression of SV40 T-antigen and the expression of ET receptor. ET-1 and fetal bovine serum stimulate DNA synthesis in non-transformed cells; however, proliferation of transformed cells is independent of either fetal bovine serum or ET-1. We conclude that SV40 transformation down-regulates the expression of ET receptors, and that expression of ET receptors is inversely correlated with expression of SV40 large T-antigen.