Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

Mammary epithelial cells from p53 null mice have been shown recently to exh ibit an increased risk for tumor development, Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid , with greater than 70% of the tumor cells containing altered chromosome nu mber and a mean chromosome number of 56, Normal mammary cells of p53 null g enotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture, Significantly, the hormone progesterone, but not estrogen, increas es the incidence of aneuploidy in morphologically normal p53 null mammary e pithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54, The increase in aneuploidy measured in p53 null tumor cells o r hormonally stimulated normal p53 null cells was not accompanied by centro some amplification. These results suggest that normal levels of progesteron e can facilitate chromosomal instability in the absence of the tumor suppre ssor gene, p53, The results support the emerging hypothesis based both on h uman epidemiological and animal model studies that progesterone markedly en hances mammary tumorigenesis.