Northern blot analysis of total RNA from the mouse C3H/10T½ cell line indicated that the erbAα 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-α2) was approximately 7- to 8-fold more abundant than either the 5.5- (erbA-α1) or 6.6-kilobase species. The expression of the erbA-α2 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-α mRNA species in confluent cells nor on the levels of erbA-α2 in proliferative normal or transformed C3H/10T½ cells. In log-phase growing cells there was a 2.5- to 5-fold increase in the relative expression of erbA-α2 mRNA in transformed mouse C3H/10T½ 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-α2 in transformed cells, erbA-α1 and erbA-β1 mRNAs decreased in transformed mouse and rat cell lines. In conclusion, it is suggested that the increased levels of the erbA-α2 transcript and the decreased levels of erbA-α1 and erbA-β1 in neoplastic cells may account for the loss of thyroid hormone regulation of inducible pathways and decreased nuclear triiodothyronine binding as previously reported.
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.