The coupling of epidermal growth factor receptor down regulation by 1alpha,25-dihydroxyvitamin D3 to the hormone-induced cell cycle arrest at the G1-S checkpoint in ovarian cancer cells.
The coupling of epidermal growth factor receptor down regulation by 1alpha,25-dihydroxyvitamin D3 to the hormone-induced cell cycle arrest at the G1-S checkpoint in ovarian cancer cells.
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DOI：
10.1016/j.mce.2011.02.023
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发表时间：
2011-05-16
影响因子：
4.1
通讯作者：
Bai, Wenlong
中科院分区：
文献类型：
--
作者：
Shen, Zheng;Zhang, Xiaohui;Tang, Jinfu;Kasiappan, Ravi;Jinwal, Urnesh;Li, Pengfei;Hann, Shan;Nicosia, Santo V.;Wu, Jie;Zhang, Xiaohong;Bai, Wenlong
1alpha,25-dihydroxyvitamin D3, 1,25(OH)2D3, regulates gene expression through the vitamin D receptor. The present studies identify the epidermal growth factor receptor, EGFR, as a target gene suppressed by 1,25(OH)2D3 in human ovarian cancer cells. The suppression was detected at both mRNA and protein levels in vitamin D-sensitive human ovarian cancer cells. A novel vitamin D response element was identified in intron 1 of the EGFR genome, a known hotspot for its transcriptional regulation. Chromatin immunoprecipitations and reporter gene analyses showed that the intronic DNA element bound to vitamin D receptor and a co-repressor and was functional in mediating transcriptional suppression of EGFR promoter by 1,25(OH)2D3 under stable transfection conditions. Consistent with the EGFR down regulation, 1,25(OH)2D3 suppressed activation of the external signal regulated kinase by epidermal growth factors. Over expression of an active EGFR in vitamin D sensitive ovarian cancer cells caused resistance to 1,25(OH)2D3-induced growth suppression and diminished the hormonal regulation of cyclin D1, cyclin E, Skp2 and p27, a group of cell cycle regulators that mediate 1,25(OH)2D3-induced cell cycle arrest at G1-S checkpoint. Taken together, our studies demonstrate that 1,25(OH)2D3 suppresses the response of human ovarian cancer cells to mitogenic growth factors and couple the suppression to the cell cycle arrest at G1-S checkpoint by the hormone.
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影响因子：
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