POSTTRANSCRIPTIONAL REGULATION OF ALBUMIN AND ALPHA-FETOPROTEIN MESSENGER-RNA BY TRANSFORMING GROWTH FACTOR-BETA-1 REQUIRES DENOVO RNA AND PROTEIN-SYNTHESIS

Transforming growth factor-beta (TGFbeta) has been implicated in the regulation of hepatocyte function. We have examined TGFbeta1 regulation of albumin and alpha-fetoprotein (AFP) mRNA levels in a well differentiated mouse hepatoma cell line (BWTG3). TGFbeta1 reversibly decreased steady state mRNA levels of both albumin and AFP. By nuclear run-on assays, we found that TGFbeta1 caused no significant change in transcription rates for albumin or AFP. Pretreatment with actinomycin-D prevented the TGFbeta1-induced decrease in albumin and AFP mRNA levels. Also, if cells were treated with actinomycin-D after a 12-h exposure to TGFbeta1, actinomycin-D abrogated the further decrease in albumin and AFP mRNA levels that occurred after treatment with TGFbeta1 alone. Cycloheximide pretreatment blocked the TGFbeta1-induced decrease in albumin and AFP mRNA levels. TGFbeta1 altered neither the rate of BWTG3 cell growth nor the levels of mRNA for the growth-associated protooncogene c-myc. These data suggest that TGFbeta1 has regulatory effects on specific hepatocyte functions that are independent of growth regulatory effects. The decrease in albumin and AFP mRNAs caused by TGFbeta1 is posttranscriptional and dependent upon de novo RNA and protein synthesis.