Altered Regulation of Intercellular Communication by Epidermal Growth Factor, Transforming Growth Factor-Beta and Peptide Hormones in Normal Human Keratinocytes

摘要

Since many chemical tumor promoters and some oncogens have been shown to inhibit gap junction-mediated intercellular communication, the effect of various growth factors on gap junctional intercellular communication on normal human keratinocytes was examined. In order to measure the effect of the growth factors on gap junctional communication, the scrape loading/dye transfer technique was used on human keratinocytes grown in a serum-free medium in vitro. At 24 h after treatment epidermal growth factor transforming growth factor-Beta, whole bovine pituitary extract and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) inhibited intercellular communication. In order to study the possible mechanism by which the growth factors might inhibit intercellular communication, the effect of the growth factors on protein kinase C activation and alterations of intracellular free calcium was investigated. The results indicated that neither protein kinase C nor an increase in (Ca2+)i were involved in the modulation of gap junctional communication by epidermal growth factor or transforming growth factor-Beta. The study suggests that in the human keratinocytes inhibition of intercellular communication may be involved (i) in the action of growth factors such as epidermal growth factor during cellular proliferation and (ii) in the differentiation of primary keratinocytes by transforming growth factor-Beta. Reprints. (AW)