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 EGFR is not required for papilloma formation initiated by a mutant rasHa gene, although the tumors that develop are very small (A. A. Dlugosz et aL, Cancer Res., 57: 3180-3188, 1997). The current study used a combination of bromodeoxyuridine pulse-chase, proliferating cell nuclear antigen distribution, and differentiation marker analysis to reveal the following: (a) the EGFR was required to maintain the proliferative population in the basal cell compartment of papillomas; (b) in the absence of EGFR, cycling tumor cells migrated into the suprabasal compartment and initiated the differentiation program prematurely; and (c) these changes were associated with cell cycle arrest. Further analysis of v-rasHa-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 pathway in squamous tumors is to maintain a proliferative pool of basal cells and prevent premature terminal differentiation.
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892, USA.
L A
LA
Hansen
R L
RL
Woodson
S
S
Holbus
K
K
Strain
Y C
YC
Lo
S H
SH
Yuspa
D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D011905:Genes, ras; D006133:Growth Substances / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D010212:Papilloma / Q000235:genetics / Q000473:pathology*; D016196:S Phase; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology*
C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D066246:ErbB Receptors