Molecular Characterization of Squamous Cell Carcinomas Derived from Recessive Dystropic Epidermolysis Bullosa

摘要

Patients with recessive dystrophic epidermolysis bullosa (RDEB) frequently present with squamous cell carcinomas (SCCs) probably as a result of chronic blistering and extensive scarring. These tumors are clinically aggressive as they metastasize readily. The metastasis-associated protein (MTA)- l, a transcription suppressor, is overexpressed in several epithelial neoplasms including SCCs. Our preliminary results demonstrate that MTAl expression is induced by - activation of the epidermal growth factor receptor (EGFR) . As deregulation of EGFR signaling is frequently observed in aggressive epithelial- neoplasms we propose to study the role of EGFR signaling and MTAl expression in SCCs derived in RDEB patients. Our Specific Aims are to establish cell lines derived from SCCs in non-RDEB and RDEB patients, characterize the malignant phenotype of these cells as it relates-to EGFR expression and signaling and to- expression of MTAl, examine the contribution of EGFR/MTAl to proliferation, invasiveness, and cell survival and identify EGFR-dependent signaling pathways contributing to MTAl expression in these cells. The results from this research- will provide invaluable tools for future analysis of the pathobiology of carcinoma cells and will ascertain whether EGFR/MTAl signaling pathways contributes significantly to the metastasis and invasiveness of SCC derived from RDEB patients.