Cellular responses to TGFβ and TGFβ receptor expression in human colonic epithelial cells require CaSR expression and function

CaSR and TGF beta are robust promoters of differentiation in the colonic epithelium. Loss of cellular responses to TGF beta or loss of CaSR expression is tightly linked to malignant progression. Human colonic epithelial CBS cells, originally developed from a differentiated human colon tumor, retain CaSR expression and function, TGF beta responsiveness and TGF beta receptor expression. Thus, these cells offer a unique opportunity in determining the functional linkage (if any) between CaSR and TGF beta. Knocking down CaSR expression abrogated TGF beta-mediated cellular responses and attenuated the expression of TGF beta receptors. Ca2+ or vitamin D treatment induced CaSR expression with a concurrent up-regulation of TGF beta receptor expression. Ca2+ or vitamin D, however, did not induce CaSR in CaSR knocked down cells and without CaSR; there was no up-regulation of TGF beta receptor. It is concluded that TGF beta receptor expression and TGF beta mediated responses requires CaSR expression and function. (C) 2013 Elsevier Ltd. All rights reserved.