There is an increasing trend to treat specific cancers with cell-specific or pathway-specific antagonists.  Although second most frequent skin cancer, the molecular mechanisms underlying development and progression of cutaneous SCC remains unclear.  We has been studying SCC on the basis of differentially expressed gene list generated by the combination of laser capture microdissection and cDNA microarray technology.  One transcription factor that was significantly upregulated in actinic keratosis, a known pre-cancerous condition, and SCC compared to normal epidermis was E2F4 (FCH>15 and FDR<10-4).  E2F4 is a member of the E2F family of transcription factors that have a critical role in the control of cellular proliferation and apoptosis.  Recent studies identified the roles of E2F4 in cancer, including breast carcinoma, prostate cancer, and melanoma.  However, its roles in SCC have not been studied to date.  In this study, we aimed to elucidate the functions of E2F4 in development and progression of cutaneous SCC.  To achieve this, we first evaluated and compared the expression of E2F4 in various skin conditions. The specific expression of E2F4 in the nucleus of SCC tissues but not in other skin conditions, such as basal cell carcinoma (BCC), seborrheic keratosis, and psoriasis was identified by immunohistochemistry.  We further confirmed that SCC cell lines (A431 and HSC-5) expressed E2F4 at genomic and protein levels.  Our results suggest that E2F4 may have some functions in development and progression of cutaneous SCC.

Analysis of the expression of a transcription factor, E2F4, in cutaneous squamous cell carcinoma (SCC)