MSH receptors and function in amelanotic B16 melanoma cells.
The possible mechanisms for the reduced melanin content and poor melanogenic response to MSH was investigated in B16-F10DD differentiation deficient melanoma cells. In particular, the MSH receptor status and associated signal transduction pathway linking to tyrosinase activity in these cells was studied for evidence of any defects. F10DD cells contained high-affinity binding sites for alpha-MSH, with KD values similar to those previously reported for other variants of the B16 melanoma. SDS-PAGE analysis after radioactive ligand cross-linking showed no evidence of gross structural alterations of the receptor. The F10DD cells expressed approximately twice as many receptors as the F10 parent cell line, suggesting a possible feedback response attempting to compensate for the amelanotic condition. The functional integrity of the MSH receptors in F10DD cells was confirmed by the presence of increased levels of cAMP in response to MSH stimulation. These results, coupled with the observation that F10 and F10DD cells express similar levels of tyrosinase mRNA and protein, point to a structural defect in tyrosinase or in the post-translational control mechanisms by which the activity of this enzyme is regulated.
Cancer Research Unit, University of Newcastle upon Tyne Medical School, UK.
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Lunec
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Pieron
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MacNeil
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Thody
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D007700:Kinetics; D008543:Melanins / Q000378:metabolism; D008546:Melanoma, Experimental / Q000209:etiology / Q000503:physiopathology* / Q000648:ultrastructure*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D011979:Receptors, Pituitary Hormone / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured; D000521:alpha-MSH / Q000494:pharmacology
D008543:Melanins; D011979:Receptors, Pituitary Hormone; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000521:alpha-MSH; C029446:MSH receptor; D000242:Cyclic AMP; D014442:Monophenol Monooxygenase