Effect of extracellular calcium on regucalcin expression and cell viability in neoplastic and non-neoplastic human prostate cells

Extracellular calcium (Ca2 +o) and its receptor, the Ca2 +-sensing receptor (CaSR), play an important role in prostate physiology, and it has been shown that the deregulation of Ca2 + homeostasis and the overexpression of CaSR are involved in prostate cancer (PCa). Regucalcin (RGN), a Ca2 +-binding protein that plays a relevant role in intracellular Ca2 + homeostasis, was identified as an under-expressed protein in human PCa. Moreover, RGN was associated with suppression of cell proliferation, suggesting that the loss of RGN may favor development and progression of PCa. This work aims to unveil the role of Ca2 +o on RGN expression and viability of non-neoplastic (PNT1A) and neoplastic (LNCaP) prostate cell lines. It was demonstrated that Ca2 +o up-regulates RGN expression in both cell lines, but important differences were found between cells for dose- and time-responses to Ca2 +o treatment. It was also shown that high [Ca2 +]o triggers different effects on cell proliferation of neoplastic and non-neoplastic PCa cells, which seems to be related with RGN expression levels. This suggests the involvement of RGN in the regulation of cell proliferation in response to Ca2 +o treatment. Also, the effect of Ca2 +o on CaSR expression seems to be dependent of RGN expression, which is strengthened by the fact that RGN-knockdown in PNT1A cells increases the CaSR expression, whereas transgenic rats overexpressing RGN exhibit low levels of CaSR. Overall, our results highlighted the importance of RGN as a regulatory protein in Ca2 +-dependent signaling pathways and its deregulation of RGN expression by Ca2 +o may contribute for onset and progression of PCa.