Calcium-dependent c-myc proto-oncogene expression and proliferation of Caco-2 cells: a role for a luminal extracellular calcium-sensing receptor

Biochem Biophys Res Commun. 1997 Mar 6;232(1):80-3. doi: 10.1006/bbrc.1997.6225.

Abstract

The human colonic cell line Caco-2 responds to a reduction of ambient [Ca++]o to levels at and below 0.25 mM by a twofold increase in [3H]thymidine labelling of their DNA. [Ca++]o signals sensed preferentially across the luminal aspect of Caco-2 cells, are rapidly (4 h) transduced via PKC activation into up to sixfold increases in c-myc expression. This suggests the presence of a [Ca++]o-sensing membrane receptor (CaR) similar to that described by Brown et al. (1) in parathyroid and kidney cells. By RT-PCR we were able to amplify a 426 bp fragment from Caco-2 mRNA with 98% nucleotide identity to a part of the coding region for the extracellular domain of the parathyroid CaR. Immunohistochemical staining with a monoclonal antiparathyroid CaR antibody demonstrates CaR protein at the plasma membrane of confluent Caco-2 cells. Our results imply that the intestinal CaR is a potential mediator for the transduction of low luminal [Ca++]o into tumor promoting signals in human colonocytes.

Publication types

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

MeSH terms

  • Caco-2 Cells
  • Calcium / metabolism*
  • Cell Division*
  • Enzyme Activation
  • Gene Expression Regulation*
  • Genes, myc*
  • Humans
  • Polymerase Chain Reaction
  • Protein Kinase C / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction

Substances

  • RNA, Messenger
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface
  • Protein Kinase C
  • Calcium