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

• Published in: Cancer research (Chicago, Ill.) Vol. 60; no. 13; pp. 3328 - 3332
• Main Authors: HANSEN, L. A, WOODSON, R. L, HOLBUS, S, STRAIN, K, LO, Y.-C, YUSPA, S. H
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.2000
• Subjects: Animal tumors. Experimental tumors; Animals; Animals, Newborn; Biological and medical sciences; Cell Cycle - physiology; Cell Transformation, Neoplastic; Experimental skin tumors; Fibroblast Growth Factor 10; Fibroblast Growth Factor 7; Fibroblast Growth Factors; Genes, ras; Growth Substances - pharmacology; Keratinocytes - cytology; Keratinocytes - drug effects; Medical sciences; Mice; Mice, Knockout; Papilloma - genetics; Papilloma - pathology; Receptor, Epidermal Growth Factor - deficiency; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - physiology; S Phase; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Tumors; Squamous cell carcinoma; Deficiency; Cytokine; Rodentia; Malignant tumor; Carcinogenesis; Cell motility; Vertebrata; Mammalia; Epidermal growth factor; Mouse; Polypeptide; Animal; Cell cycle; Keratinocyte; Papilloma; Skin; Benign neoplasm; Ras gene; Growth factor; Biological receptor
• ISSN: 0008-5472; 1538-7445

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.