The Role of Estrogen in the Regulation of EGFR Expression

Abstract

In breast cancer, epidermal growth factor receptor (EGFR) expression is inversely correlated with expression of estrogen receptor (ER) (Fitzpatrick et al. 1984; Sainsbury et al. 1985; Koenders et al. 1991; Sharma et al. 1992). While expression of ER usually predicts for responsiveness to endocrine therapy and overall good prognosis (Osborne et al. 1980), EGFR expression (independent of ER) correlates with lack of response to endocrine therapy, high incidence of metastasis, and poor survival (Koenders et al. 1991; Toi et al. 1991; Nicholson et al. 1994; Fox et al. 1994). This raises the possibility that EGFR provides an alternative growth pathway that cells are able to utilize in the absence of estrogen. An inverse correlation between ER and EGFR expression is also found in breast cancer cell lines, with ER-positive breast cancer cells expressing very low levels of EGFR (Davidson et al. 1987). Moreover, many cell regulators such as EGF, 12-O-tetradecanoyl phorbol acetate (TPA), and sodium butyrate have opposite effects on the expression of the two receptors (Lee et al. 1989; Secada et al. 1991; De Fazio et al. 1992). This well-established inverse correlation between EGFR and ER expression led us to hypothesize that estrogen may play an active role in maintaining low levels of EGFR expression in ER-positive breast cancer cells.