Extracellular calcium and calcium sensing receptor function in human colon carcinomas: promotion of E-cadherin expression and suppression of beta-catenin/TCF activation.
Ca(2+) has chemopreventive activity against colon cancer, albeit its mechanisms of action are not understood. In this study, we showed that four different human colon carcinoma cell lines (FET, SW480, MOSER, and CBS) expressed the human parathyroid calcium sensing receptor (CaSR) and that a function of extracellular Ca(2+) and the CaSR in these cells was the promotion of E-cadherin expression and suppression of beta-catenin/T cell factor activation. We also found that human colonic crypt epithelial cells expressed the CaSR, and histologically differentiated carcinomas (i.e., where three-dimensional, crypt-like structures were present) expressed less receptor by comparison, whereas an almost complete loss of CaSR expression was observed in undifferentiated tumors. These results suggest that extracellular Ca(2+) and the CaSR may function to regulate the differentiation of colonic epithelial cells and that disruption of this ligand receptor system may contribute to abnormal differentiation and malignant progression. In addition, the promotion of E-cadherin and suppression of beta-catenin/T cell factor may be an important mechanism underlying the chemopreventive action of Ca(2+) in colon cancer.
Chakrabarty
Subhas
S
Department of Molecular Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. schakrab@mdanderson.org
Radjendirane
Venugopal
V
Appelman
Henry
H
Varani
James
J
D015820:Cadherins / Q000235:genetics*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000503:physiopathology*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008222:Lymphokines / Q000235:genetics*; D015345:Oligonucleotide Probes; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D008222:Lymphokines; D015345:Oligonucleotide Probes; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D051176:beta Catenin; D002118:Calcium