Posttranscriptional regulation of albumin and alpha-fetoprotein messenger RNA by transforming growth factor-beta 1 requires de novo RNA and protein synthesis

Mol Endocrinol. 1992 Nov;6(11):1789-96. doi: 10.1210/mend.6.11.1282669.

Abstract

Transforming growth factor-beta (TGF beta) has been implicated in the regulation of hepatocyte function. We have examined TGF beta 1 regulation of albumin and alpha-fetoprotein (AFP) mRNA levels in a well differentiated mouse hepatoma cell line (BWTG3). TGF beta 1 reversibly decreased steady state mRNA levels of both albumin and AFP. By nuclear run-on assays, we found that TGF beta 1 caused no significant change in transcription rates for albumin or AFP. Pretreatment with actinomycin-D prevented the TGF beta 1-induced decrease in albumin and AFP mRNA levels. Also, if cells were treated with actinomycin-D after a 12-h exposure to TGF beta 1, actinomycin-D abrogated the further decrease in albumin and AFP mRNA levels that occurred after treatment with TGF beta 1 alone. Cycloheximide pretreatment blocked the TGF beta 1-induced decrease in albumin and AFP mRNA levels. TGF beta 1 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 beta 1 has regulatory effects on specific hepatocyte functions that are independent of growth regulatory effects. The decrease in albumin and AFP mRNAs caused by TGF beta 1 is posttranscriptional and dependent upon de novo RNA and protein synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albumins / biosynthesis*
  • Albumins / genetics
  • Animals
  • Depression, Chemical
  • Gene Expression Regulation, Neoplastic
  • Liver / drug effects*
  • Liver / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Mice
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / metabolism
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured
  • alpha-Fetoproteins / biosynthesis*
  • alpha-Fetoproteins / genetics

Substances

  • Albumins
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Transforming Growth Factor beta
  • alpha-Fetoproteins