The Contribution of 17beta-Hydroxysteroid Dehydrogenase Type 1 to the Estradiol-Estrone Ratio in Estrogen-Sensitive Breast Cancer Cells

	The Contribution of 17beta-Hydroxysteroid Dehydrogenase Type 1 to the Estradiol-Estrone Ratio in Estrogen-Sensitive Breast Cancer Cells
	Zhang, CY; Chen, J; Yin, DC; Lin, SX
刊名	PLOS ONE
	2012
卷号	7 期号:1 页码:e29835-e29835
通讯作者	Lin, SX (reprint author), CHUQ, CHU Laval, Lab Mol Endocrinol & Oncol, Res Ctr, Quebec City, PQ, Canada.,sheng-xiang.lin@crchul.ulaval.ca
英文摘要	Estrone and estradiol are both estrogens with estrone being the less potent form and estradiol being the most potent estrogen. The binding of the latter to cellular regulatory elements stimulates the proliferation of breast cancer cells. A high ratio of estradiol/estrone is related to increased cell proliferation, and is of great importance to understanding of breast cancer mechanisms. 17beta-hydroxysteroid dehydrogenase type 1 and type 2 play important roles in the activation of estrone and inactivation of estradiol. Breast cancer cells T47D, MCF-7, BT 20, and JEG 3 as control cells, were chosen to evaluate the contribution of these two enzymes to the ratio. Twenty four hours after addition of different concentrations of estrone and estradiol, the ratio stabilized to around 9/1 in breast cancer cell lines with high expression of type 1 (T47D, BT 20, and JEG 3), whereas it approached 1/5 in cells with low expression of type 1 (MCF-7). The estradiol/estrone concentration ratio was modified to 9/1 in MCF-7 and HEK-293 cells over-expressing type 1. In T47D and BT 20, this ratio was decreased from 9/1 to nearly 1/5 (19/81 and 17/83 respectively) after type 1 knockdown by specific siRNAs. Type 2 is mainly involved in the conversion of estradiol into estrone. This ratio was decreased from 9/1 to 7/3 after over-expression of type 2 in MCF-7 cells already over-expressing type 1. The ratio was further decreased by the addition of the oxidative cofactor, NAD, to the cell culture to facilitate the estradiol to estrone conversion catalyzed by type 2. These results demonstrate that the estradiol/estrone ratio is controlled by both type 1 and type 2 with an additional contribution by NAD, although type 1 is the first determining factor in the cellular environment compared with type 2 and cofactors. Moreover, kinetic studies were carried out in intact cells as a new approach, using HEK-293 cells over-expressing type 1 and T47D breast cancer cells.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	HUMAN 17-BETA-HYDROXYSTEROID DEHYDROGENASES ; HEK-293 CELLS ; EXPRESSION ; SULFATASE ; ENZYMES ; PROLIFERATION ; METABOLISM ; REDUCTION ; PREDICTS ; NADPH
收录类别	SCI
语种	英语
WOS记录号	WOS:000315865800017
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/527]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhang, CY,Chen, J,Yin, DC,et al. The Contribution of 17beta-Hydroxysteroid Dehydrogenase Type 1 to the Estradiol-Estrone Ratio in Estrogen-Sensitive Breast Cancer Cells[J]. PLOS ONE,2012,7(1):e29835-e29835.
APA	Zhang, CY,Chen, J,Yin, DC,&Lin, SX.(2012).The Contribution of 17beta-Hydroxysteroid Dehydrogenase Type 1 to the Estradiol-Estrone Ratio in Estrogen-Sensitive Breast Cancer Cells.PLOS ONE,7(1),e29835-e29835.
MLA	Zhang, CY,et al."The Contribution of 17beta-Hydroxysteroid Dehydrogenase Type 1 to the Estradiol-Estrone Ratio in Estrogen-Sensitive Breast Cancer Cells".PLOS ONE 7.1(2012):e29835-e29835.