PMID- 28176351 OWN - NLM STAT- MEDLINE DCOM- 20180326 LR - 20181022 IS - 1099-1263 (Electronic) IS - 0260-437X (Linking) VI - 37 IP - 8 DP - 2017 Aug TI - Role of connexin 43 in cadmium-induced proliferation of human prostate epithelial cells. PG - 933-942 LID - 10.1002/jat.3441 [doi] AB - Connexins (Cxs), the subunits of gap junction channels, are involved in many physiological processes. Aberrant control of Cxs and gap junction intercellular communication may contribute to many diseases, including the promotion of cancer. Cd exposure is associated with increased risk of human prostate cancer and benign prostatic hyperplasia. The roles of Cxs in the effects of Cd on the prostate have, however, not been reported previously. In this study, the human prostate epithelial cell line RWPE-1 was exposed to Cd. A low dose of Cd stimulated cell proliferation along with a lower degree of gap junction intercellular communication and an elevated level of the protein Cx43. Cd exposure increased the levels of intracellular Ca(2+) and phosphorylated Cx43 at the Ser368 site. Knockdown of Cx43 using siRNA blocked Cd-induced proliferation and interfered with the Cd-induced changes in the protein levels of cyclin D1, cyclin B1, p27(Kip1) (p27) and p21(Waf1/Cip1) (p21). The increase in Cx43 expression induced by Cd was presumably mediated by the androgen receptor, because it was abolished upon treatment with the androgen receptor antagonist, flutamide. Thus, a low dose of Cd promotes cell proliferation in RWPE-1, possibly mediated by Cx43 expression through an effect on cell cycle-associated proteins. Cx43 might be a target for prostatic diseases associated with Cd exposure. Copyright (c) 2017 John Wiley & Sons, Ltd. CI - Copyright (c) 2017 John Wiley & Sons, Ltd. FAU - Liu, Qingping AU - Liu Q AD - School of Public Health, Fudan University, DongAn Road, Shanghai, 200032, China. AD - Key Laboratory of Public Health Safety, Ministry of Education, DongAn Road, Shanghai, 200032, China. FAU - Ji, Xiaoli AU - Ji X AD - School of Public Health, Fudan University, DongAn Road, Shanghai, 200032, China. AD - Key Laboratory of Public Health Safety, Ministry of Education, DongAn Road, Shanghai, 200032, China. FAU - Ge, Zehe AU - Ge Z AD - School of Public Health, Fudan University, DongAn Road, Shanghai, 200032, China. AD - Key Laboratory of Public Health Safety, Ministry of Education, DongAn Road, Shanghai, 200032, China. FAU - Diao, Haipeng AU - Diao H AD - School of Public Health, Fudan University, DongAn Road, Shanghai, 200032, China. AD - Key Laboratory of Public Health Safety, Ministry of Education, DongAn Road, Shanghai, 200032, China. FAU - Chang, Xiuli AU - Chang X AD - School of Public Health, Fudan University, DongAn Road, Shanghai, 200032, China. AD - Key Laboratory of Public Health Safety, Ministry of Education, DongAn Road, Shanghai, 200032, China. FAU - Wang, Lihua AU - Wang L AD - Shanghai Jinshan District Center for Disease Control & Prevention, Weisheng Road, Jinshan District, Shanghai, 201599, China. FAU - Wu, Qing AU - Wu Q AUID- ORCID: 0000-0002-6124-2594 AD - School of Public Health, Fudan University, DongAn Road, Shanghai, 200032, China. AD - Key Laboratory of Public Health Safety, Ministry of Education, DongAn Road, Shanghai, 200032, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170208 PL - England TA - J Appl Toxicol JT - Journal of applied toxicology : JAT JID - 8109495 RN - 0 (Connexin 43) RN - 0 (Environmental Pollutants) RN - 0 (GJA1 protein, human) RN - 00BH33GNGH (Cadmium) SB - IM MH - Apoptosis/drug effects MH - Cadmium/*toxicity MH - Cell Communication/drug effects MH - Cell Culture Techniques MH - Cell Cycle/drug effects MH - Cell Line MH - Cell Proliferation/*drug effects MH - Connexin 43/genetics/*metabolism MH - Dose-Response Relationship, Drug MH - Environmental Pollutants/*toxicity MH - Epithelial Cells/*drug effects/metabolism/pathology MH - Gap Junctions/drug effects/metabolism MH - Gene Knockdown Techniques MH - Humans MH - Male MH - Prostate/*drug effects/metabolism/pathology OTO - NOTNLM OT - Cx43 OT - GJIC OT - androgen receptor OT - cadmium OT - cell proliferation OT - prostate EDAT- 2017/02/09 06:00 MHDA- 2018/03/27 06:00 CRDT- 2017/02/09 06:00 PHST- 2016/10/25 00:00 [received] PHST- 2016/12/21 00:00 [revised] PHST- 2016/12/23 00:00 [accepted] PHST- 2017/02/09 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2017/02/09 06:00 [entrez] AID - 10.1002/jat.3441 [doi] PST - ppublish SO - J Appl Toxicol. 2017 Aug;37(8):933-942. doi: 10.1002/jat.3441. Epub 2017 Feb 8.