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

Laura A. Hansen, Roderick L. Woodson, Sherry Holbus, Kathryn Strain, You Chein Lo, Stuart H. Yuspa

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Abstract

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 ras(Ha) 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 pulsechase, 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-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 pathway in squamous tumors is to maintain a proliferative pool of basal cells and prevent premature terminal differentiation.

Original languageEnglish
Pages (from-to)3328-3332
Number of pages5
JournalCancer Research
Volume60
Issue number13
Publication statusPublished - Jul 1 2000
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

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