Reconstitution of the G_s protein from B16 melanoma clones of high and low experimental metastatic potential into S49 cyc^- membranes

The ability of a series of B16 melanoma clones to form experimental lung metastases in syngeneic mice has been shown to correlate positively with adenylate cyclase activity. (^{Sheppard et al, Int. J. Cancer 37 (1986) 713-722}). To begin to identify the components of the adenylate cyclase complex that account for enhanced enzyme activity in highly metastatic tumor populations, cholate extracts containing the GTP-binding protein G_s from B16 melanoma clones of different metastatic capacities were reconstituted with membranes prepared from S49 cyc^-, a variant lymphoma cell line that lacks G_s function. The results revealed that extracts from a highly metastatic B16 clone (F10-C23) reconstituted significantly greater adenylate cyclase activities in S49 cyc^- membranes than parallel preparations from a B16 clone (F1-C29) of low metastatic capacity. The data suggest that aberrations in G_s function may contribute to the heightened responsiveness of adenylate cyclase observed in B16 melanoma clones of increased metastatic potential.