Human mammary epithelial cells exhibit a differential p53-mediated response following exposure to ionizing radiation or UV light
Human mammary epithelial cells exhibit a differential p53-mediated response following exposure to ionizing radiation or UV light
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DOI：
10.1038/sj.onc.1202977
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发表时间：
1999-10-14
期刊：
影响因子：
8
通讯作者：
Leadon, SA
中科院分区：
文献类型：
--
作者：
Meyer, KM;Hess, SM;Leadon, SA
肿瘤抑制蛋白p53作为下游靶基因的转录激活因子发挥着关键作用，该基因参与对DNA损伤剂的细胞反应。我们检查了人乳腺上皮细胞（HMEC）及其同基因成纤维细胞对应物对电离（IR）的细胞周期检查点反应。和紫外线（UV）辐射，这两种遗传毒性物质的DNA损伤反应途径涉及p53，使用流式细胞仪分析，我们发现，无论是致命的和永生化的HMEC，其中包含野生型p53序列，不表现出G1期阻滞在IR响应，但显示一个完整的G2检查点。Western分析的支持性证据显示，在暴露于IR的HMEC中，p53及其下游靶点p21（WAF 1）均未增加。相反，IR后，同基因乳腺成纤维细胞在G1检查点停滞并诱导p53和p21（WAF 1）蛋白。紫外线照射HMEC后，HMEC细胞出现S期阻滞，并诱导p53和p21（WAF 1）的表达。我们的研究结果表明，细胞对DNA损伤的反应取决于引入DNA的损伤类型和特定的细胞类型。
The tumor suppressor protein, p53, plays a critical role as a transcriptional activator of downstream target genes involved in the cellular response to DNA damaging agents, We examined the cell cycle checkpoint response of human mammary epithelial cells (HMEC) and their isogenic fibroblast counterparts to ionizing (IR) and ultraviolet (UV) radiation, two genotoxic agents whose DNA damage response pathways involve p53, Using flow cytometric analysis, we found that both mortal and immortalized HMEC, which contain wild-type p53 sequence, do not exhibit a G1 arrest in response to IR, but show an intact G2 checkpoint. Supportive evidence from Western analyses revealed that there was neither an increase in p53 nor one of its downstream targets, p21(WAF1), in HMEC exposed to IR. In contrast, isogenic mammary fibroblasts arrest at the G1 checkpoint and induce the p53 and p21(WAF1) proteins following 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 cellular response to DNA damage depends on both the type of damage introduced into the DNA and the specific cell type.