PKC epsilon Overexpression, Irrespective of Genetic Background, Sensitizes Skin to UVR-Induced Development of Squamous-Cell Carcinomas

Chronic exposure to UVR is the major etiologic factor in the development of human skin cancers including squamous-cell carcinoma (SCC). We have previously shown that protein Kinase C epsilon (PKC epsilon) transgenic mice on FVB/N background, which overexpress PKC epsilon protein approximately eightfold over endogenous levels in epidermis, exhibit about threefold more sensitivity than wild-type littermates to UVR-induced development of SCC. To determine whether it is PKC epsilon and not the mouse genetic background that determines susceptibility to UVR carcinogenesis, we cross-bred PKC epsilon FVB/N transgenic mice with SKH-1 hairless mice to generate PKC epsilon-overexpressing SKH-1 hairless mice. To evaluate the susceptibility of PKC epsilon SKH-1 hairless transgenic mice to UVR carcinogenesis, the mice were exposed to UVR (1-2 KJm(-2)) three times weekly from a bank of six kodacel-filtered FS40 sunlamps. As compared with the wild-type hairless mice, PKC epsilon overexpression in SKH-1 hairless mice decreased the latency (12 weeks), whereas it increased the incidence (twofold) and multiplicity (fourfold) of SCC. The SKH hairless transgenic mice were observed to be as sensitive as FVB/N transgenic mice to UVR-induced development of SCC and expression of proliferative markers (proliferating cell nuclear antigen, signal transducers and activators of transcription 3, and extracellular signal-regulated kinase 1/2). The results indicate that PKC epsilon level dictates susceptibility, irrespective of genetic background, to UVR carcinogenesis.