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Increased Messenger RNA Levels of the Antagonist Thyroid Hormone Receptor erbA-2 and Decreased Levels of erbA-1 and erbA-ß1 Receptor Messenger RNAs in Neoplastic Rodent Cells¹

Department sof Pathology [C. K. L. T., D. L. G.] and Physiology & Biophysics [D. L. G.], Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7

Northern blot analysis of total RNA from the mouse C3H/10T cell line indicated that the erbA gene transcribed three mRNA species of similar sizes (2.6, 5.5, 6.6 kilobases) as found in rodents. The 2.6-kilobase mRNA (erbA-2) was approximately 7- to 8-fold more abundant than either the 5.5- (erbA-1) or 6.6-kilobase species. The expression of the erbA-2 transcript increased 3- to 30-fold when "normal" mouse or rat cells were growth arrested by confluence. Triiodothyronine, at a concentration of 1 nM, had no effect on the levels of the erbA- mRNA species in confluent cells nor on the levels of erbA-2 in proliferative normal or transformed C3H/10T cells. In log-phase growing cells there was a 2.5- to 5-fold increase in the relative expression of erbA-2 mRNA in transformed mouse C3H/10T cells, transformed cloned rat embryo fibroblasts (CREF), transformed rat embryo fibroblasts (REF), and a transformed temperature-sensitive rat mutant cell line (ts7E) when compared with their non-transformed counterparts. In contrast to the elevation of erbA-2 in transformed cells, erbA-1 and erbA-ß1 mRNAs decreased in transformed mouse and rat cell lines. In conclusion, it is suggested that the increased levels of the erbA-2 transcript and the decreased levels of erbA-1 and erbA-ß1 in neoplastic cells may account for the loss of thyroid hormone regulation of inducible pathways and decreased nuclear triiodothyronine binding as previously reported.

¹ This work was supported by the National Cancer Institute of Canada (Grant 1618), the Dalhousie Medical Research Foundation, and the Dalhousie University Faculty of Medicine.

Received 9/30/91. Accepted 2/10/92.