Human mammary epithelial cells exhibit a differential p53-mediated response following exposure to ionizing radiation or UV light

The tumor suppressor protein, p53, plays a critical role as a transcription al activator of downstream target genes involved in the cellular response t o DNA damaging agents, We examined the cell cycle checkpoint response of hu man mammary epithelial cells (HMEC) and their isogenic fibroblast counterpa rts to ionizing (IR) and ultraviolet (UV) radiation, two genotoxic agents w hose DNA damage response pathways involve p53, Using flow cytometric analys is, we found that both mortal and immortalized HMEC, which contain wild-typ e p53 sequence, do not exhibit a G1 arrest in response to IR, but show an i ntact G2 checkpoint. Supportive evidence from Western analyses revealed tha t there was neither an increase in p53 nor one of its downstream targets, p 21(WAF1), in HMEC exposed to IR. In contrast, isogenic mammary fibroblasts arrest at the G1 checkpoint and induce the p53 and p21(WAF1) proteins follo wing IR, By comparison, HMEC exposed to UV displayed an S phase arrest and induced the expression of p53 and p21(WAF1). Our results show that the cell ular response to DNA damage depends on both the type of damage introduced i nto the DNA and the specific cell type.