Protein-kinase-Cμ expression correlates with enhanced keratinocyte proliferation in normal and neoplastic mouse epidermis and in cell culture

✍ Scribed by Jörg Rennecke; Petra Andrea Rehberger; Gerhard Fürstenberger; Franz-Josef Johannes; Michael Stöhr; Friedrich Marks; Karl Hartmut Richter

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 137 KB
• Volume: 80
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990105)80:1<98::aid-ijc19>3.0.co;2-d

✦ Synopsis

In order to gain insight into the biological function of a PKC iso-enzyme, the protein kinase C, we analyzed the expression pattern of this protein in mouse epidermis and keratinocytes in culture. Daily analysis of neonatal mouse epidermis immediately after birth showed a time-dependent reduction in the PKC content. Expression of the proliferating-cell nuclear antigen (PCNA), indicative of the proliferative state of cells, was reduced synchronously with PKC as the hyperplastic state of the neonatal tissue declined. In epidermal mouse keratinocytes, fractionated according to their maturation state, PKC expression was restricted to PCNA-positive basal-cell fractions. In primary cultures of those cells, growth arrest and induction of terminal differentiation by Ca 2؉ resulted in strongly reduced PKC expression, concomitantly with the loss of PCNA expression. Treatment of PMK-R1 keratinocytes with 100 nM of the mitogen 12-Otetradecanoylphorbol-13-acetate (TPA) resulted in activation of PKC, reflected by translocation from the cytosolic to the particulate fraction and by shifts in electrophoretic mobility. DNA synthesis was significantly inhibited by the PKC inhibitor Goedecke 6976, while Goedecke 6983 did not inhibit PKC. Carcinomas generated according to the 2-stage carcinogenesis protocol in mouse skin consistently exhibited high levels of PKC. These data correlate PKC expression with the proliferative state of murine keratinocytes and point to a role of PKC in growth stimulation. A correlation between PKC expression and enhanced cell proliferation was also observed for NIH3T3 fibroblasts transfected with and overexpressing human PKC. Int.