Evidence that TRPM7 is required for breast cancer cell proliferation.
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 Mg(2+)-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 Mg(2+) or Mg(2+)-ATP. The inward current was reduced by La(3+), and the outward current was sensitive to 2-aminoethoxydiphenyl borate (2-APB), spermine, La(3+), 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 Ca(2+) 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 Ca(2+) influx.
Guilbert
Arnaud
A
Laboratoire de Physiologie Cellulaire et Moléculaire, Univ. Picardie Jules Verne, Faculté des Sciences, 33 Rue St Leu, 80000 Amiens, France.
Gautier
Mathieu
M
Dhennin-Duthille
Isabelle
I
Haren
Nathalie
N
Sevestre
Henri
H
Ouadid-Ahidouch
Halima
H
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008345:Manganese; D008564:Membrane Potentials / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D046509:Tissue Culture Techniques
D050053:TRPM Cation Channels; D008345:Manganese; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D008274:Magnesium; D002118:Calcium