COMPARISON OF RATES OF PHENOTYPIC VARIABILITY IN SURFACE-ANTIGEN EXPRESSION IN NORMAL AND CANCEROUS HUMAN-BREAST EPITHELIAL-CELLS

Abstract

A method is described for measuring the rate of phenotypic variability in normal and neoplastic breast epithelial cells. Three groups of normal human mammary epithelial cases were studied, 2 derived from reduction mammoplasties and 1 derived from the normal breast tissue of a patient with fibroadenoma. The breast carcinoma cells were all cell lines, 4 (MCF-7, SKBR-3, MDA-MB-157 and T47D) derived from pleural effusions of patients with breast cancer, and 1 (BT-20) derived from a primary breast tumor. The heterogeneity and variability in expression of a cell surface glycoprotein with apparent MW of 400,000 were studied at the single-cell level with immunoperoxidase techniques using a specific monoclonal antibody, BLMRL-HMFG-Mc5, to a nonpenetrating glycoprotein. The rate of appearance of quantitative variants in expression of this specific surface antigen (rate of phenotypic variability) was determined in clonal colonies and was several-fold higher in all 5 breast carcinoma cell lines (mean 2.23 .times. 10-2/cell per generation) than in the normal breast epithelial cells (mean, 0.36 .times. 10-2/cell per generation). A considerable quantitative variation in expression of this surface antigen was demonstrated among the cells of each population in both normal and neoplastic breast cells which spread over an 8- to 10-fold range. The quantitative distribution among single cells was not random, for the cells tended to cluster around values that fit a geometric series.