SV40 virus transformation down-regulates endothelin receptor.
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 ETA and ETB 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 ETA and ETB 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 degrees C) than at the restrictive temperature (40 degrees 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.
Chiou
W J
WJ
Pharmaceutical Products Division, D-47H, AP9A, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Wang
J
J
Berg
C E
CE
Wu-Wong
J R
JR
D000957:Antigens, Viral, Tumor / Q000032:analysis / Q000096:biosynthesis*; D001665:Binding Sites; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D019332:Endothelin-1 / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D017466:Receptors, Endothelin / Q000096:biosynthesis / Q000378:metabolism*; D013539:Simian virus 40
D000957:Antigens, Viral, Tumor; D019332:Endothelin-1; D012333:RNA, Messenger; D017466:Receptors, Endothelin