CALCIUM-DEPENDENT C-MYC PROTOONCOGENE EXPRESSION AND PROLIFERATION OFCACO-2 CELLS - A ROLE FOR A LUMINAL EXTRACELLULAR CALCIUM-SENSING RECEPTOR

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 [H-3 ]thymidine labelling of their DNA. [Ca++](o) signals sensed preferenti ally across the luminal aspect of Caco-2 cells, are rapidly (4 h) tran sduced via PKC activation into up to sixfold increases in c-myc expres sion. This suggests the presence of a [Ca++](o)-sensing membrane recep tor (CaR) similar to that described by frown 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. Immunohis tochemical staining with a monoclonal anti-parathyroid CaR antibody de monstrates CaR protein at the plasma membrane of confluent Caco-2 cell s, Our results imply that the intestinal CaR is a potential mediator f or the transduction of low luminal [Ca++](o) into tumor promoting sign als in human colonocytes. (C) 1997 Academic Press.