Calcium-dependent c-myc proto-oncogene expression and proliferation of Caco-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 [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.
Kállay
E
E
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
Kifor
O
O
Chattopadhyay
N
N
Brown
E M
EM
Bischof
M G
MG
Peterlik
M
M
Cross
H S
HS
D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D016259:Genes, myc; D006801:Humans; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D011493:Protein Kinase C; D002118:Calcium