Down-regulation of Orai3 arrests cell-cycle progression and induces apoptosis in breast cancer cells but not in normal breast epithelial cells

作者: Malika Faouzi , Frederic Hague , Marie Potier , Ahmed Ahidouch , Henri Sevestre

DOI: 10.1002/JCP.22363

关键词:

摘要: Breast cancer (BC) is the leading in world terms of incidence and mortality women. However, mechanism by which BC develops remains largely unknown. The increase cytosolic free Ca(2+) can result different physiological changes including cell growth death. Orai isoforms are highly selective channels. In present study, we analyzed Orai3 expression normal cancerous breast tissue samples, its role MCF-7 MCF-10A mammary epithelial lines. We found that mRNAs was higher tissues cells than cells. Down-regulation siRNA inhibited proliferation arrested cycle at G1 phase. This phenomenon associated with a reduction CDKs 4/2 (cyclin-dependent kinases) cyclins E D1 an accumulation p21(Waf1/Cip1) (a cyclin-dependent kinase inhibitor) p53 tumor-suppressing protein). also involved survival. Furthermore, mediated entry contributed to intracellular calcium concentration ([Ca(2+)](i)). cells, silencing failed modify [Ca(2+)](i), proliferation, cell-cycle progression, (D1, E), (4, 2), expression. Our results provide strong evidence for significant effect on vitro show this induction apoptosis resistance. study highlights possible as therapeutic target therapy.

参考文章(62)
Silvio Veronese, Francesco A. Mauri, Orazio Caffo, Monica Scaioli, Daniela Aldovini, Giorgio Perrone, Enzo Galligioni, Claudio Doglioni, Paolo Dalla Palma, Mattia Barbareschi, Bax immunohistochemical expression in breast carcinoma: a study with long term follow-up. International Journal of Cancer. ,vol. 79, pp. 13- 18 ,(1998) , 10.1002/(SICI)1097-0215(19980220)79:1<13::AID-IJC3>3.0.CO;2-Z
Jonathan Soboloff, Maria A Spassova, Xiang D Tang, Thamara Hewavitharana, Wen Xu, Donald L Gill, None, Orai1 and STIM reconstitute store-operated calcium channel function. Journal of Biological Chemistry. ,vol. 281, pp. 20661- 20665 ,(2006) , 10.1074/JBC.C600126200
Murali Prakriya, Stefan Feske, Yousang Gwack, Sonal Srikanth, Anjana Rao, Patrick G. Hogan, Orai1 is an essential pore subunit of the CRAC channel Nature. ,vol. 443, pp. 230- 233 ,(2006) , 10.1038/NATURE05122
Andriy V. Yeromin, Shenyuan L. Zhang, Weihua Jiang, Ying Yu, Olga Safrina, Michael D. Cahalan, Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai Nature. ,vol. 443, pp. 226- 229 ,(2006) , 10.1038/NATURE05108
Rong Cai, Xia Ding, Kechun Zhou, Yu Shi, Ruiliang Ge, Gang Ren, Yening Jin, Yizheng Wang, Blockade of TRPC6 channels induced G2/M phase arrest and suppressed growth in human gastric cancer cells. International Journal of Cancer. ,vol. 125, pp. 2281- 2287 ,(2009) , 10.1002/IJC.24551
Rajender K. Motiani, Iskandar F. Abdullaev, Mohamed Trebak, A Novel Native Store-operated Calcium Channel Encoded by Orai3 Journal of Biological Chemistry. ,vol. 285, pp. 19173- 19183 ,(2010) , 10.1074/JBC.M110.102582
D. V. Hansen, J. J. Tung, P. K. Jackson, CaMKII and Polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit Proceedings of the National Academy of Sciences of the United States of America. ,vol. 103, pp. 608- 613 ,(2006) , 10.1073/PNAS.0509549102
A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray, M. J. Thun, Cancer statistics, 2008. CA: A Cancer Journal for Clinicians. ,vol. 58, pp. 71- 96 ,(2008) , 10.3322/CA.2007.0010
Jason C. Mercer, Wayne I. DeHaven, Jeremy T. Smyth, Barbara Wedel, Rebecca R. Boyles, Gary S. Bird, James W. Putney, Large Store-operated Calcium Selective Currents Due to Co-expression of Orai1 or Orai2 with the Intracellular Calcium Sensor, Stim1 Journal of Biological Chemistry. ,vol. 281, pp. 24979- 24990 ,(2006) , 10.1074/JBC.M604589200
David Cobrinik, Pocket proteins and cell cycle control. Oncogene. ,vol. 24, pp. 2796- 2809 ,(2005) , 10.1038/SJ.ONC.1208619