NERVE GROWTH-FACTOR REGULATES TRANSFORMING GROWTH-FACTOR-BETA-1 GENE-EXPRESSION BY BOTH TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MECHANISMS IN PC12 CELLS

PC12 cells express two transforming growth factor(TGF)-beta 1 transcri pts, 1.7 and 2.5 kb in size. Other TGF-beta s are expressed at much lo wer levels. Incubation with nerve growth factor (NGF) produced a time- and dose-dependent increase in content of TGF-beta 1 transcripts. The level of the smaller mRNA increased little, whereas that of the 2.5-k b transcript increased more, with the latter becoming the predominant TGF-beta 1 message. NGF differentially regulated the stability of both mRNAs. The half-life of the 2.5-kb transcript was not altered by NGF; however, the half-life of the 1.7-kb mRNA was similar to 6 h and incr eased to >30 h on incubation with NGF. In addition, induction of the 2 .5-kb TGF-beta 1 mRNA by NGF required de novo protein synthesis, where as induction of the 1.7-kb TGF-beta 1 mRNA was independent of protein synthesis. The NGF effect was independent of protein kinase C activati on, which also preferentially induced the larger transcript. PC12 cell s release a significant amount of TGF-beta 1, and incubation with NGF further increases TGF-beta 1 production, This factor is released in a latent form. These results indicate that an increase in expression and secretion of TGF-beta 1 accompanies neuronal differentiation in PC12 cells. Regulation of TGF-beta 1 gene expression by NGF is complex, inv olving both increased transcription of the TGF-beta 1 gene and stabili zation of the smaller TGF-beta 1 transcript.