title: Cellular responses to TGFβ and TGFβ receptor expression in human colonic epithelial cells require CaSR expression and function.
abstract: CaSR and TGFβ are robust promoters of differentiation in the colonic epithelium. Loss of cellular responses to TGFβ 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, TGFβ responsiveness and TGFβ receptor expression. Thus, these cells offer a unique opportunity in determining the functional linkage (if any) between CaSR and TGFβ. Knocking down CaSR expression abrogated TGFβ-mediated cellular responses and attenuated the expression of TGFβ receptors. Ca²⁺ or vitamin D treatment induced CaSR expression with a concurrent up-regulation of TGFβ 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 TGFβ receptor. It is concluded that TGFβ receptor expression and TGFβ mediated responses requires CaSR expression and function.
authors: Simmons Cancer Institute and Department Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794-9677, USA.
authors: Navneet
authors: N
authors: Singh
authors: Guangming
authors: G
authors: Liu
authors: Subhas
authors: S
authors: Chakrabarty
mesh_terms: D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014807:Vitamin D / Q000494:pharmacology
chemical_list: D034741:RNA, Small Interfering; D044169:Receptors, Calcium-Sensing; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014807:Vitamin D; D002118:Calcium