AP: Murine colonic mucosa hyperproliferation. I. Elevated CFTR expression and enhanced cAMPdependent Cl(−) secretion

trointest Liver Physiol 278: G753–G764, 2000.—Fluid trans-port in the large intestine is mediated by the cystic fibrosis gene product and cAMP-dependent anion channel cystic fibrosis transmembrane conductance regulator (CFTR). cAMP-mediated Cl2 secretion by gastrointestinal cell lines in vitro has been positively correlated with the insertion of CFTR into the apical membrane of differentiated senescent colonocytes and negatively correlated with the failure of CFTR to insert into the plasma membrane of their undifferentiated prolifer-ating counterparts. In native tissues, this relationship re-mains unresolved. We demonstrate, in a transmissible mu-rine colonic hyperplasia (TMCH) model, that (8-fold) colonocyte proliferation was accompanied by increased cellu-lar CFTR mRNA and protein expression (8.3- and 2.4-fold, respectively) and enhanced mucosal cAMP-dependent Cl