title: Isolation and characterization of a variant of B16-mouse melanoma resistant to MSH growth inhibition.
abstract: A variant of B-16 F1 mouse melanoma was selected for its ability to survive and replicate in the presence of melanocyte-stimulating hormone (MSH). Although the variant (MR-4) was completely resistant to growth inhibition of MSH, cyclic AMP was still able to block cell replication. Tyrosinase activity in MR-4 cells was considerably lower than in B-16 F1 cells. MSH induced a two fold to three-fold increase in tyrosinase activity in both cell types, but the absolute activity in MR-4 remained significantly less than in the parental cells. MR-4 cells were also found to have a markedly depressed cyclic AMP-dependent protein kinase activity relative to B-16 F1 cells. The protein kinase from both cell types was stimulated by cyclic AMP, but the level of MR-4 kinase activity at maximal cyclic AMP concentrations remained considerably lower than B-16 F1 kinase activity under the same conditions. In both cell types adenylate cyclase activity was markedly stimulated by MSH. When equal numbers of viable F1 and MR-4 cells were injected subcutaneously into C57/B1 mice, the MR-4 cells formed tumors earlier and killed the host sooner than the parental F1 cells. We conclude that the biochemical alteration which allows MR-4 cells to replicate in the presence of MSH is a low level of tyrosinase activity, which in turn may be the result of low cyclic AMP-dependent protein kinase activity.
mesh_terms: D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D000242:Cyclic AMP / Q000032:analysis; D009074:Melanocyte-Stimulating Hormones / Q000627:therapeutic use*; D008545:Melanoma / Q000032:analysis / Q000188:drug therapy* / Q000201:enzymology; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009374:Neoplasms, Experimental; D011494:Protein Kinases / Q000378:metabolism
chemical_list: D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase; D011494:Protein Kinases