c-erbA Protooncogenes Mediate Thyroid Hormone-Dependent and Independent Regulation of the Rat Growth Hormone and Prolactin Genes

Barry Marc Forman, Chang-ren Yang, Frederick Stanley, Juan Casanova, Herbert H. Samuels
1988 Molecular Endocrinology  
Regulation of gene expression by the thyroid hormones is thought to be mediated by a nuclearassociated receptor found in a wide variety of cells and tissues. Cellular homologues of the avian erythroblastosis virus oncogene , v-erbA, encode proteins which bind thyroid hormone with similar affinities as thyroid hormone receptors. However, it has not been shown that any of the c-erbA proteins can function as receptor and modulate thyroid hormone responsive genes. In this study, using transient
more » ... using transient expression of chimeric reporter constructs, we document that the chick fibroblast c-erbA-a and the human placental c-erbA-/? modulate c/s-acting regulatory sequences of two thyroid hormone responsive genes; rat GH and PRL. From these results we conclude: 1) in a receptor deficient cell line (235-1) both c-erbA subtypes act as hormone-dependent modulators of PRL gene expression and hence function as thyroid hormone receptors, 2) in two different receptor containing cell lines (GH4C1 and GHi), both c-erbA proteins act in a hormone-independent fashion to regulate PRL and GH expression. This suggests that events other than ligand binding can result in formation of a c-erbA protein that modulates transcription of thyroid hormone responsive genes, 3) no qualitative functional differences were detected between a-and 0-c-erbA subtypes, and 4) depending on the cell-type, L-T 3 acts through its endogenous receptor to stimulate (GH4C1) or suppress (GH n ) expression of a chimeric PRL construct. In these .cells, c-erbA expression results in the same positive or negative response as the endogenous receptor except that the response occurs in the absence of hormone. These results suggest that the endogenous receptor and the c-erbAs act by augmenting the effect of transcription factors which can posi-0888-8809/88/0902-0911 $02.00/0 Molecular Endocrinology Copyright© 1988 by The Endocrine Society tively or negatively control gene expression. (Molecular Endocrinology 2: 902-911,1988)
doi:10.1210/mend-2-10-902 pmid:2903439 fatcat:7eh55t656rbrjgfdiopq5mp53m