CONICET | Buscador de Institutos y Recursos Humanos

Parathyroid hormone (PTH) and Calcitriol (1α,25(OH)2 Vitamin D3) are essential regulators of calcium homeostasis. Depending on cellular context, both hormones may also be related with apoptosis and/or cell proliferation and even with cell cycle regulation. Previously, we demonstrated that PTH (10 -8 M) exerts pro-apoptotic and anti-proliferative effects in human colon cell line Caco-2 while others authors observed that the treatment with Calcitriol at doses above 10 -10 M induces anti-proliferative effects in these cells. Moreover, previous studies showed that in prostate cancer cells, Calcitriol induces the anti-proliferative response through down-regulation of PTHrP expression. Recently we found that exogenous PTHrP promotes the survival, proliferation and migration of Caco-2 cells. Based on these findings, this study is aimed to evaluate if the response of Caco-2 cells to PTH or Calcitriol occurs through the modulation of PTHrP expression. We found by qPCR assay that PTH treatment for 5 h increases PTHrP mRNA levels. However, at 24 h of PTH exposure, these levels were similar to those observed in control cells. Exposition to PTH for 4 days followed by proliferation assay revealed a significant difference in the number of live cells between Caco-2 cells overexpressing PTHrP respect to control cells suggesting that PTH exerts its anti-proliferative role through the control of PTHrP expression. Then we found by qPCR assay that Calcitriol at the times studied (5-48 h) down-regulates the expression of PTHrP. However, the number of live cells was similar when both, Caco-2 cells overexpressing PTHrP and control cells were exposed to Calcitriol, suggesting that PTHrP does not participate in the effect of this hormone on Caco-2 cells. These results expand our knowledge about the molecular mechanisms that mediate the action of calciotropic hormones on tumor intestinal cells.