Objectives: 

Intracellular calcium plays a critical role in control of short-term and long-term cell functions including cell proliferation. In particular, the store-operated calcium entry pathway (SOCE), that is activated by Ca2+ release from intracellular stores and modulated by mitochondria, has been involved in cell proliferation. In some cell types, the molecular basis of SOCE involves Stim1, a endoplasmic reticulum calcium sensor and Orai1, a component of the calcium-release activated current (CRAC). Recent data suggest that increased proliferation and survival of tumor cells may rely on remodeling of calcium channels. In addition, pharmacological inhibition of SOCE may prevent tumor cell proliferation. Here, we aimed to investigate remodeling of SOCE and its molecular players Stim1 and Orai1 in human colon adenocarcinoma cells relative to normal colonic mucosa cells.

Materials: 

Cell counting and calcium imaging was used for testing cell proliferation and SOCE in human colon adenocarcinoma cells (HT29 cells) and human normal colonic mucosa cells (NCM460 cells). Quantitative RT-PCR and western blotting were employed in the same cells for assessing expression of SOCE molecular players Stim1 and Orai1.

Results: 

We found that colon carcinoma proliferated at a higher rate than normal colon mucosa cells. This functional difference correlated with increased SOCE in tumor cells relative to normal, non transformed cells. Interestingly, tumor cells expressed more Orai1 and Stim1 mRNAs and protein than normal cells.

Conclusions: 

In conclusion, our results suggest that increased SOCE and cell proliferation characteristic of tumor cells are related to increased expression of CRAC molecular components.

This work was funded by DIGICYT (BFU2009-08967 and Junta de Castilla y León, Spain (VA270A11-2). DS and EM were recipients of a JAE and FPI fellowships, respectively. The NCM460 cell line was received by a material transfer agreement with INCELL corporation, San Antonio, TX.