Overexpression of Protein Kinase C-α in the Epidermis of Transgenic Mice Results in Striking Alterations in Phorbol Ester-Induced Inflammation and COX-2, MIP-2, and TNF-α Expression but Not Tumor Promotion

The study investigated the effects of overexpressing protein kinase Cα (PKCα) in the epidermis of transgenic mice. PKCα was primarily expressed in the outer root sheath keratinocytes of hair follicles. Transgenic mice with increased PKCα expression showed no changes in keratinocyte growth or differentiation. However, when treated with the PKC activator TPA, these mice exhibited a significant inflammatory response, including edema and neutrophil infiltration, leading to microabscesses. This response was associated with increased expression of COX-2, MIP-2, and TNFα, but not IL-6 or IL-1α. Despite these inflammatory changes, there was no difference in tumor promotion between transgenic and wild-type mice, indicating that PKCα overexpression heightened inflammation without affecting tumor development.