Submitted on December 8, 2008
Revised on June 3, 2009
Accepted on June 3, 2009
Evidence that TRPM7 is required for breast cancer cell proliferation
Arnaud Guilbert1, Mathieu Gautier2, Isabelle Dhennin-Duthille1, Nathalie HAREN3, Henri Sevestre4, and Halima Ouadid-Ahidouch5*
1 UPJV
2 Universite tours
3 UPJV, Amiens
4 UJPV/CHU Amiens
5 Universit Picardie Jules Verne, Facult des Sciences
* To whom correspondence should be addressed. E-mail: ha-sciences{at}u-picardie.fr.
Because Transient Receptor Potential (TRP) channels have been implicated in tumour 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 which 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 MCF7 cells, the MIC current was inhibited by small interfering RNA-TRPM7. Interestingly, we found that cell proliferation and [Ca2+]in 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 over-expressed in grade III breast cancer samples associated with important Ki67 or tumour size. Our findings strongly suggest that TRPM7 is involved in the proliferative potentiality of breast cancer cells, probably by regulating the Ca2+ influx.
