Abstract
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.
Highlights
Ca2+ is a ubiquitous messenger that has been shown to be responsible for controlling numerous cellular processes including cell growth and cell death
We show that the expression level of IP3R3 is controlled by E2 in an estrogen receptor-dependent manner and that the growth of MCF-7 cells induced by E2 is sensitive to pharmacological inhibitors of IP3 receptor (IP3R)
Serum and E2 trigger Ca2+ release from inositol 1 (IP3)-sensitive stores As for many other cell types, the growth of MCF-7 cells is dependent on internal Ca2+ and these cells are able to elicit intracellular Ca2+ signals in response of multiple ligands [31]
Summary
Ca2+ is a ubiquitous messenger that has been shown to be responsible for controlling numerous cellular processes including cell growth and cell death. Ca2+ is a ubiquitous messenger that has been shown to be responsible for controlling numerous cellular processes including muscle contraction, exocytosis, gene expression, cell growth and cell death [1,2,3]. IP3R protein subtypes (namely IP3R1, IP3R2 and IP3R3) are encoded by three different genes in mammals but share high similarity in their primary sequences and are expressed to varying degrees in various cell types [12] Even though they share common properties, it has been shown, that they are responsible for different types of Ca2+ signals when expressed alone [13,14]. It has been shown that the encoding of several genes is dependent on the oscillatory or transitory pattern of the Ca2+ signal [16,17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
