Abstract:
:We have described a family of adrenocortical tumor cell mutants (including clones OS3, Y6, and 10r9) that are resistant to ACTH because they fail to express the gene encoding the ACTH receptor (MC2R). The MC2R deficiency results from a mutation that impairs the activity of the nuclear receptor steroidogenic factor 1 (SF1) at the MC2R promoter. In this report, we show that ACTH resistance in the mutant clones is associated with a Sf1 gene that has Ser at codon 172 instead of Ala. In two of the three mutant clones, this Sf1 allele is amplified together with flanking DNA from chromosome 2 that includes the genes encoding germ cell nuclear factor and the beta-type proteosome subunit Psmb7. SF1(A172) and SF1(S172) exhibit little or no difference in transcriptional activity in SF1-dependent reporter gene assays, suggesting that SF1(S172) per se is not directly responsible for the loss of MC2R expression. Instead, the Sf1(S172) allele appears to be a marker of ACTH resistance in this family of adrenocortical tumor cell mutants, possibly reflecting the activity of a neighboring gene.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Schimmer BP,Cordova M,Tsao J,Frigeri Cdoi
10.1111/j.1749-6632.2003.tb03174.xsubject
Has Abstractpub_date
2003-06-01 00:00:00pages
147-53eissn
0077-8923issn
1749-6632journal_volume
994pub_type
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