Frequent allelic imbalance on chromosome 6 and 17 correlate with radiation-induced neoplastic transformation of human breast epithelial cells

The development of human breast cancer is a complex multi-step process that depends on various exogenous and endogenous factors that modulate the tran sformation of normal human breast epithelial cells into neoplastic ones. Us ing a spontaneously-immortalized human breast epithelial (MCF-10F) cell lin e, we have shown previously that radiation, in combination with estrogen, i nduces a stepwise neoplastic transformation of this cell line. In the prese nt study, we investigate the incidence of microsatellite instability and lo ss of heterozygosity using a battery of markers on chromosomes 6 and 17, we correlate the genetic alteration with the malignant transformation of the MCF-10F cell line ranging from altered morphology to increase in proliferat ive rate, anchorage independent growth and tumorigenicity in nude mice. Mic rosatellite markers were selected from the hot spot regions (6q21-q27, 17p1 2-p13.3 and 17q12-q21) of both chromosomes. We found that the frequency of allelic imbalance occurs at the different stages of tumor progression with a range of 21 to 50% depending on the marker studied. The relatively high r ate of allele imbalance at all these loci suggests the presence and inactiv ation of one or more tumor suppressor genes in these regions. Thus, the pre sent data will be useful for systematic studies to identify the cellular an d molecular changes associated with radiation-induced breast carcinogenesis .