Inositol 1,4,5-trisphosphate-induced Ca2+ signalling is involved in estradiol-induced breast cancer epithelial cell growth

Molecular Cancer

Research

Jan B Parys¹  Halima Ouadid-Ahidouch²  Cécilia Szatkowski²  Fabrice Matifat² 

[1] Department of Molecular and Cellular Biology, Laboratory of Molecular and Cellular Signalling, Campus Gasthuisberg O/N1- bus 802 - K U Leuven, Herestraat 49, B-3000, Leuven, Belgium;Laboratoire de Physiologie Cellulaire et Moléculaire - JE-2530: Canaux ioniques et cancer du sein, Université d'Amiens, UFR des Sciences, 33 rue Saint-Leu, 80039, Amiens, France;

关键词: Caffeine;    Area Under Curve;    Iberiotoxin;    Breast Cancer Epithelial Cell;    Human Breast Cancer Epithelial Cell;   

DOI  :  10.1186/1476-4598-9-156

 received in 2009-10-21, accepted in 2010-06-21,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundCa2+ is a ubiquitous messenger that has been shown to be responsible for controlling numerous cellular processes including cell growth and cell death. Whereas the involvement of IP3-induced Ca2+ signalling (IICS) in the physiological activity of numerous cell types is well documented, the role of IICS in cancer cells is still largely unknown. Our purpose was to characterize the role of IICS in the control of growth of the estrogen-dependent human breast cancer epithelial cell line MCF-7 and its potential regulation by 17β-estradiol (E2).ResultsOur results show that the IP3 receptor (IP3R) inhibitors caffeine, 2-APB and xestospongin C (XeC) inhibited the growth of MCF-7 stimulated by 5% foetal calf serum or 10 nM E2. Furthermore, Ca2+ imaging experiments showed that serum and E2 were able to trigger, in a Ca2+-free medium, an elevation of internal Ca2+ in a 2-APB and XeC-sensitive manner. Moreover, the phospholipase C (PLC) inhibitor U-73122 was able to prevent intracellular Ca2+ elevation in response to serum, whereas the inactive analogue U-73343 was ineffective. Western-blotting experiments revealed that the 3 types of IP3Rs are expressed in MCF-7 cells and that a 48 hours treatment with 10 nM E2 elevated IP3R3 protein expression level in an ICI-182,780 (a specific estrogen receptor antagonist)-dependent manner. Furthermore, IP3R3 silencing by the use of specific small interfering RNA was responsible for a drastic modification of the temporal feature of IICS, independently of a modification of the sensitivity of the Ca2+ release process and acted to counteract the proliferative effect of 10 nM E2.ConclusionsAltogether, our results are in favour of a role of IICS in MCF-7 cell growth, and we hypothesize that the regulation of IP3R3 expression by E2 is involved in this effect.

【 授权许可】

Unknown   
© Szatkowski et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.