CONSTITUTIVE MUCIN SECRETION LINKED TO CFTR EXPRESSION

Mucus plugging is a hallmark of cystic fibrosis, but the link between the defective gene the cystic fibrosis transmembrane conductance regul ator, and the abnormal mucus phenotype is unclear. To demonstrate CFTR involvement in mucin glycoprotein secretion in epithelial cells, a re troviral vector was used to overexpress CFTR in gallbladder epithelial cells, and constitutive mucin labeling and secretion were monitored. Achievement of high-level vector expression was confirmed by transduct ion with marker genes. Cells transduced with vectors carrying CFTR cDN A showed 5-fold increased expression of CFTR by Western blotting. Muci n labeling and secretion were 4-fold elevated in transduced cells. The se results suggest constitutive mucin synthesis and secretion in gallb ladder epithelial cells are regulated by CFTR. (C) 1994 Academic Press , Inc.