IN-VITRO KARYOTYPE EVOLUTION AND CYTOGENETIC INSTABILITY IN THE NONTUMORIGENIC HUMAN BREAST EPITHELIAL-CELL LINE HMT-3522

The ''spontaneously'' immortalized cell line HMT-3522, derived from a fibrocystic breast lesion, is used as a model for premalignant breast epithelium. During 205 passages the cytogenetic evolution was followed. The results were compared with our earlier results on oncogene expression and growth factor requirements. During in vitro growth, gain and loss of markers, loss of normal chromosomes, and duplication of the chromosome complement could be demonstrated. The variability increased during in vitro growth. This variability, probably created randomly, leads to cells with different growth capacities, from which sidelines may be selected and become stemlines. The karyotypic evolution (including polyploidization) demonstrated here may be a result of genetic instability and heterogeneity. Although tumorigenicity was not achieved, either due to lack of cancer-specific gene alterations or to lack of proper selection pressure, the results suggest an ongoing process towards malignancy.