TY - JOUR
T1 - The epidermal growth factor receptor is required to maintain the proliferative population in the basal compartment of epidermal tumors
AU - Hansen, Laura A.
AU - Woodson, Roderick L.
AU - Holbus, Sherry
AU - Strain, Kathryn
AU - Lo, You Chein
AU - Yuspa, Stuart H.
PY - 2000/7/1
Y1 - 2000/7/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 10910032
AN - SCOPUS:0034235628
VL - 60
SP - 3328
EP - 3332
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 13
ER -