EPIDERMAL GROWTH-FACTOR BINDING BY BREAST-TUMOR BIOPSIES AND RELATIONSHIP TO ESTROGEN-RECEPTOR AND PROGESTIN RECEPTOR LEVELS

Abstract

Epidermal growth factor (EGF) may be important in regulating the growth of some breast cancer cells in vivo because of its mitogenic action on some breast cancer cell lines in vitro. Epidermal growth factor receptors (EGF-R) were measured in a series of breast tumors to determine what percentage of breast tumors express EGF-R and whether EGF-R was independent of expression of estrogen receptor [ER] and progestin receptor. Specific binding of 125I-EGF to membranes from pooled homogenates of breast tumors reached equilibrium after 45 min at 25.degree. and remained constant. Scatchard analysis of 125I-EGF binding indicated a single class of receptors with an apparent Kd of 2 nM and a binding capacity of 28 fmol/mg of membrane protein. The binding of 125I-EGF was not effectively competed for by insulin, fibroblast growth factor, growth hormone or prolactin. Specific binding of 125I-EGF or 1 fmol or greater/mg of membrane protein and 15% greater specific binding was detected in 48% of 137 unselected primary and metastatic breast tumors. The frequency distribution of EGF binding values was unimodal, with a progressive decrease in the proportion of patients with high EGF binding values. The values of EGF binding ranged from 1-121 fmol/mg of protein, with an arithmetic mean of 8.4 fmol/mg of protein and a geometric mean of 3.2 fmol/mg of protein. Of 24 metastatic breast tumors, 42% were positive for EGF binding, with an arithmetic mean of 6.3 fmol/mg of protein and a geometric mean of 4.1 fmol/mg of protein. The magnitude of EGF binding in individual tumors was independent of either estrogen receptor of progestin receptor levels, although the highest quantities of EGF binding were expressed by tumors lacking steroid receptors. Approximately 20% of the tumors in the study were EGF-R-positive and ER-negative, suggesting that the growth of these tumors may be regulated predominantly by a peptide hormone (EGF) rather than a steroid hormone (estrogen). EGF binding did not correlate significantly with age of the patients. Correlation analysis between EGF binding and the percentage of malignant and nonmalignant cell types present in sections of tumor adjacent to the area assayed for EGF binding indicated that the percentage of malignant cells is an important factor in determining the amount of EGF binding in tumor homogenates. The recent discovery of transforming growth factors which interact with the EGF-receptor system suggests additional roles for EGF receptors in breast cancer.