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 expre ssion and growth factor requirements. During in vitro growth, gain and loss of markers, loss of normal chromosomes, and duplication of the c hromosome complement could be demonstrated. The variability increased during in vitro growth. This variability, probably created randomly, l eads to cells with different growth capacities, from which sidelines m ay be selected and become stemlines. The karyotypic evolution (includi ng polyploidization) demonstrated here may be a result of genetic inst ability and heterogeneity. Although tumorigenicity was not achieved, e ither due to lack of cancer-specific gene alterations or to lack of pr oper selection pressure, the results suggest an ongoing process toward s malignancy.