Extracellular Signal-Regulated Kinases 1 and 2 and TRPC1 Channels are Required for Calcium-Sensing Receptor-Stimulated MCF-7 Breast Cancer Cell Proliferation - Archive ouverte HAL Access content directly
Journal Articles Cellular Physiology and Biochemistry Year : 2009

Extracellular Signal-Regulated Kinases 1 and 2 and TRPC1 Channels are Required for Calcium-Sensing Receptor-Stimulated MCF-7 Breast Cancer Cell Proliferation

(1) , (1, 2) , (3) , (1) , (3) , (4) , (4) , (3) , (1) , (1)
1
2
3
4

Abstract

The calcium-sensing receptor (CaR), is a G protein-dependent receptor that responds to increments in extracellular Ca(2+) ([Ca(2+)](o)). We previously reported that an increase in [Ca(2+)](o) induced a release of intracellular calcium and Ca(2+) entry via store operated channels (SOCs). We also demonstrated that MCF-7 cells express Transient Receptor Potential canonical 1 (TRPC1) channels. Herein, we investigated CaR intracellular signaling pathways and examined the role of TRPC1 in CaR-induced cell proliferation, through the extracellular signal-regulated Kinases 1 & 2 (ERK1/2) pathways. Treatment by [Ca(2+)](o) increased both MCF-7 cell proliferation and TRPC1 expression. Both the [Ca(2+)](o) proliferative effect and TRPC1 protein levels were abolished by the ERK1/2 inhibitors. Moreover, [Ca(2+)](o) failed to increase cell proliferation either in the presence of CaR or TRPC1 siRNAs. Both [Ca(2+)](o) and the selective CaR activator spermine, elicited time and dose-dependent ERK1/2 phosphorylation. ERK1/2 phosphorylation was almost completely inhibited by treatment with the phospholipase C and the protein kinase C inhibitors. Treatment with 2-aminoethoxydiphenyl borate (2-APB), and SKF-96365 or by siTRPC1 diminished both [Ca(2+)](o)- and spermine-stimulated ERK1/2 phosphorylation. Moreover, down-regulation of TRPC1 by siRNA reduced the Ca(2+) entry induced by CaR activation. We conclude that the CaR activates ERK1/2 via a PLC/PKC-dependent pathway. Moreover, TRPC1 is required for the ERK1/2 phosphorylation, Ca(2+) entry and the CaR-proliferative effect.
Fichier principal
Vignette du fichier
Extracellular Signal-Regulated Kinases 1 and 2.pdf (827.41 Ko) Télécharger le fichier
Origin : Explicit agreement for this submission

Dates and versions

hal-02424604 , version 1 (04-11-2021)

Identifiers

Cite

Yassine El Hiani, Ahmed Ahidouch, V'Yacheslav Lehen'Kyi, Frédéric Hague, Fabrice Gouilleux, et al.. Extracellular Signal-Regulated Kinases 1 and 2 and TRPC1 Channels are Required for Calcium-Sensing Receptor-Stimulated MCF-7 Breast Cancer Cell Proliferation. Cellular Physiology and Biochemistry, 2009, 23 (4-6), pp.335-346. ⟨10.1159/000218179⟩. ⟨hal-02424604⟩
31 View
25 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More