Differential regulation of transforming growth factor alpha autoinduction in a nontransformed and transformed epithelial cell.

Coffey RJ, Graves-Deal R, Dempsey PJ, Whitehead RH, Pittelkow MR
Cell Growth Differ. 1992 3 (6): 347-54

PMID: 1419897

Addition of transforming growth factor alpha (TGF-alpha) to cultured human keratinocytes results in enhanced expression of TGF-alpha mRNA. This phenomenon of TGF-alpha autoinduction is also observed in a TGF-alpha responsive colon cancer cell line, LIM 1215. In the present study, regulation of TGF-alpha autoinduction is examined in these two cell types. In human keratinocytes, but not in LIM 1215 cells, the increase in steady-state TGF-alpha mRNA following administration of TGF-alpha is due to stabilization of the 4.8-kilobase TGF-alpha transcript, as determined by actinomycin D decay curves. Nuclear run-on experiments confirmed transcriptional control in LIM 1215 cells. Basal and TGF-alpha-stimulated TGF-alpha expression is mediated, at least in part, through a protein kinase C-dependent pathway in both cell types, as determined by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), which attenuates TGF-alpha mRNA accumulation. In the keratinocytes, but not in the LIM 1215 cells, basal TGF-alpha expression is mediated through an epidermal growth factor receptor-dependent pathway, as determined by antibody blockade of the epidermal growth factor receptor. Thus, differential regulation of TGF-alpha autoinduction exists in these nontransformed and transformed epithelial cell types.

MeSH Terms (13)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Cell Line, Transformed Colon Gene Expression Regulation, Neoplastic Humans Isoquinolines Keratinocytes Piperazines Protein Kinase C RNA, Messenger Signal Transduction Transcription, Genetic Transforming Growth Factor alpha

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