Posttranscriptional regulation of albumin and α-fetoprotein messenger RNA by transforming growth factor-β1 requires de novo RNA and protein synthesis

Transforming growth factor-β (TGF β) has been implicated in the regulation of hepatocyte function. We have examined TGF β1 regulation of albumin and β-fetoprotein (AFP) mRNA levels in a well differentiated mouse hepatoma cell line (BWTG3). TGF β1 reversibly decreased steady state mRNA levels of both albumin and AFP. By nuclear run-on assays, we found that TGF β1 caused no significant change in transcription rates for albumin or AFP. Pretreatment with actinomycin-D prevented the TGF β1-induced decrease in albumin and AFP mRNA levels. Also, if cells were treated with actinomycin-D after a 12-h exposure to TGF β1, actinomycin-D abrogated the further decrease in albumin and AFP mRNA levels that occurred after treatment with TGF β1 alone. Cycloheximide pretreatment blocked the TGF β1-induced decrease in albumin and AFP mRNA levels. TGF β1 altered neither the rate of BWTG3 cell growth nor the levels of mRNA for the growth-associated protooncogene c-myc. These data suggest that TGF β1 has regulatory effects on specific hepatocyte functions that are independent of growth regulatory effects. The decrease in albumin and AFP mRNAs caused by TGF β1 is posttranscriptional and dependent upon de novo RNA and protein synthesis.