Protein Tyrosine Kinase 6 Regulates UVB Induced Signaling and Tumorigenesis in Mouse Skin

Protein Tyrosine Kinase 6 (PTK6, also called BRK) is an intracellular tyrosine kinase expressed in the epithelial linings of the gastrointestinal tract and skin, where it is expressed in nondividing differentiated cells. We found PTK6 expression increases in the epidermis following UVB treatment. To evaluate the roles of PTK6 in the skin following UVB-induced damage, we exposed back skin of Ptk6 +/+ and Ptk6−/− SENCAR mice to incremental doses of UVB for thirty weeks. Wild type mice were more sensitive to UVB and exhibited increased inflammation and greater activation of STAT3 than Ptk6−/− mice. Disruption of Ptk6 did not have an impact on proliferation, although PTK6 was expressed and activated in basal epithelial cells in wild type mice following UVB treatment. However, wild type mice exhibited shortened tumor latency and increased tumor load compared with Ptk6−/− mice, and STAT3 activation was increased in these tumors. PTK6 activation was detected in UVB-induced tumors, and this correlated with increased activating phosphorylation of FAK and BCAR1. Activation of PTK6 was also detected in human squamous cell carcinomas of the skin. Although PTK6 plays roles in normal differentiation, it also contributes to UVB induced injury and tumorigenesis in vivo.