Decreased ETbReceptor Expression in Human Metastatic Melanoma Cells

Abstract

In this study, we examined the endothelin (ET) receptor subtype involved in mitogenic signaling in human primary and metastatic melanoma cell lines. In a reverse transcriptase–polymerase chain reaction (RT–PCR) study, ETbmRNA expression in metastatic melanoma cells was decreased from that of primary melanoma. Only RPM-EP, a primary recurrent melanoma cell line, showed strong ETamRNA expression. ET-1 and ET-3 stimulated DNA synthesis of primary and recurrent cutaneous melanoma cells in serum-deprived cultures. The growth response to ET-1 in metastatic melanoma cells was decreased from that in primary melanoma cells. [125I]-IRL-1620 binding to PM-WK, a primary melanoma cell line, was significantly blocked by excessive amounts of unlabeled BQ-788. [125I]-IRL-1620 binding to metastatic melanoma cells was significantly decreased from that of primary melanoma cells. From these results, we conclude that the mitogenic effects of ET in human primary melanoma are mainly mediated through ETbreceptors and that down-regulation of ETbreceptors causes the decreased growth response of ET-1 in metastatic melanoma cells.