Calcium-sensing receptor activating ERK1/2 and PI3K-Akt pathways to induce the proliferation of osteosarcoma cells

Clin Exp Pharmacol Physiol. 2020 Mar;47(3):517-519. doi: 10.1111/1440-1681.13209. Epub 2019 Nov 24.

Abstract

Our results showed that the expression of calcium-sensing receptor (CaSR) and the concentration of intracellular calcium were enhanced in the osteosarcoma cells MG-63 compared with in the normal osteoblasts hFOB1.19. GdCl3 (CaSR agonist) significantly increased the proliferation rate of MG-63 cells, the expression of PCNA and Cyclin D1 and decreased the expression of p21Cip/WAF-1 . The effect of NPS2390 (CaSR antagonist) on the above indicators was opposite to GdCl3 . In addition, GdCl3 up-regulated the phosphorylation of ERK1/2, PI3K and Akt and the proliferation rate of MG-63 cells. However, these effects of GdCl3 were cancelled by LY294002 (a PI3K inhibitor) or PD98059 (an ERK1/2 inhibitor). Our results demonstrate that activation of CaSR promotes osteosarcoma cell multiplication by up-regulating ERK1/2 and PI3K-Akt pathways.

Keywords: calcium-sensing receptor; osteosarcoma cells; proliferation; signalling pathway.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Receptors, Calcium-Sensing / metabolism*

Substances

  • Receptors, Calcium-Sensing
  • Proto-Oncogene Proteins c-akt