The epidermal growth factor receptor is required to maintain the proliferative population in the basal compartment of epidermal tumors

Previous studies using keratinocytes from epidermal growth factor receptor (EGFR)-deficient mice revealed that the ECFR is not required for papilloma formation initiated by a mutant ras(Ha) gene, although the tumors that deve lop are very small (A, A. Dlugosz et at, Cancer Res., 57: 3180-3188, 1997), The current study used a combination of bromodeoxyuridine pulse-chase, pro liferating cell nuclear antigen distribution, and differentiation marker an alysis to reveal the following: (a) the EGFR was required to maintain the p roliferative population in the basal cell compartment of papillomas; (b) in the absence of EGFR, cycling tumor cells migrated into the suprabasal comp artment and initiated the differentiation program prematurely; and (c) thes e changes were associated with cell cycle arrest. Further analysis of v-ras (Ha)-transformed EGFR-deficient keratinocytes in vitro indicated that such cells migrated more on and attached less to extracellular matrix components . Together, these studies reveal that an essential function for the EGFR pa thway in squamous tumors is to maintain a proliferative pool of basal cells and prevent premature terminal differentiation.