HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/C493    most recent 00624.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Guilbert, A. Articles by Ouadid-Ahidouch, H. PubMed PubMed Citation Articles by Guilbert, A. Articles by Ouadid-Ahidouch, H.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Evidence that TRPM7 is required for breast cancer cell proliferation

¹Laboratoire de Physiologie Cellulaire et Moléculaire, JE 2530: Canaux Ioniques dans le Cancer du Sein, Faculté des Sciences, and ²Service d'Anatomie Pathologique, Centre Hospitalier Universitaire Nord, Amiens, France

Submitted 8 December 2008 ; accepted in final form 3 June 2009

Because transient receptor potential (TRP) channels have been implicated in tumor progression, we have investigated the potential role of TRPM7 channel in breast cancer cell proliferation. Under whole cell patch clamp, a Mg²⁺-inhibited cationic (MIC) current was observed in MCF-7 cells. This current was characterized by an inward current and a strong outward rectifying current that were both inhibited in a concentration-dependent manner by the presence of intracellular Mg²⁺ or Mg²⁺-ATP. The inward current was reduced by La³⁺, and the outward current was sensitive to 2-aminoethoxydiphenyl borate (2-APB), spermine, La³⁺, and flufenamic acid. Importantly, a similar MIC current was also recorded in the primary culture of human breast cancerous epithelial cells (hBCE). Moreover, TRPM7 transcripts were found in both hBCE and MCF-7 cells. In MCF-7 cells, the MIC current was inhibited by TRPM7 small interfering RNA. Interestingly, we found that cell proliferation and intracellular Ca²⁺ concentration were also reduced by TRPM7 silencing in MCF-7 cells. TRPM7 channels were also found in both human breast cancer and healthy tissues. Importantly, TRPM7 channel was overexpressed in grade III breast cancer samples associated with important Ki67 or tumor size. Our findings strongly suggest that TRPM7 is involved in the proliferative potentiality of breast cancer cells, probably by regulating Ca²⁺ influx.

transient receptor potential