The pathogenesis of squamous cell cancer: lessons learned from studies of skin carcinogenesis

摘要: This study used the induction of squamous cell carcinomas on mouse skin as an experimental model to evaluate molecular and biochemical changes that contribute neoplastic phenotype. The was facilitated by development keratinocyte culture assays reproduce each stage carcinogenesis process, discoveries stage-specific genetic epigenetic application pharmacological tools modify step. An early event in transformation keratinocytes involves mutation activation rasHa gene, producing a benign tumor. phenotypic consequences ras mutations are mediated epidermal growth factor receptor (EGFR), upregulation protein kinase C (PKC)α AP-1 transcriptional activity inactivation PKCδ through tyrosine phosphorylation. These tumors manifested hyperproliferation aberrant expression genes (PKCα AP-1) delayed terminal differentiation (PKCδ). Accumulated chromosomal abnormalities, multifocal alterations gene associated with premalignant progression. Upregulation fos causes malignant conversion keratinocytes. In absence c-fos, tumor cells fail upregulate secreted angiogenic proteolytic factors this may prevent conversion. pathways provide targets for preventive strategies interrupt process prior evolution fully