ACTH-receptor deficient mutants of the Y1 mouse adrenocortical tumor cell line.
Two mutant clones (Y6 and OS3) derived from the ACTH-responsive Y1 mouse adrenocortical tumor cell line fail to respond to ACTH with increased adenylyl cyclase activity and, as a consequence, are resistant to the steroidogenic effects of the hormone. As determined from Northern blot and RNase protection assays, ACTH resistance in these mutants results from the failure to accumulate ACTH receptor transcripts. The ACTH receptor gene appears to be present in these mutants as determined by Southern blot hybridization analysis and can be activated following the growth of the mutant cells as tumors in mice, suggesting that the ACTH receptor gene is modified in a reversible manner. When mutant cells are transformed with a gene encoding the mouse beta 2-adrenergic receptor they respond to beta-adrenergic agonists with increased adenylyl cyclase activity in a manner that is indistinguishable from a similarly transformed parent Y1 cell line. These results suggest that the adenylyl cyclase system in the mutants is otherwise intact and that the failure to express ACTH receptor transcripts limits the responsiveness of these clones to the hormone.
Schimmer
B P
BP
Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
Kwan
W K
WK
Tsao
J
J
Qiu
R
R
D000262:Adenylyl Cyclases / Q000235:genetics; D000306:Adrenal Cortex Neoplasms / Q000473:pathology / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D015139:Blotting, Southern; D004351:Drug Resistance; D008745:Methylation; D051379:Mice; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D018043:Receptors, Corticotropin / Q000172:deficiency* / Q000235:genetics; D014162:Transfection; D014170:Transformation, Genetic; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D018043:Receptors, Corticotropin; D000324:Adrenocorticotropic Hormone; D000262:Adenylyl Cyclases