Epidermal growth factor receptor activity upregulates lactate dehydrogenase A expression, lactate dehydrogenase activity, and lactate secretion in cultured IB3-1 cystic fibrosis lung epithelial cells

Cystic fibrosis (CF) is caused by mutations in the cystic transmembrane conductance regulator (CFTR) gene. It has been postulated that reduced HCO 3 ? transport through CFTR may lead to a decreased airway surface liquid pH. In contrast, others have reported no changes extracellular pH (pHe). We recently carcinoma Caco-2/pRS26 cells (transfected with short hairpin RNA for CFTR) or CF lung epithelial IB3-1 cells, mutation mitochondrial complex I activity and increased lactic acid production, owing an autocrine IL-1? loop. The secreted lactate accounted pHe, because oxamate fully restored pHe. These effects were attributed loop downstream signaling kinases c-Src JNK. Here we show pHe of can be normal values (?7.4) incubation epidermal growth factor receptor (EGFR, HER1, ErbB1) inhibitors AG1478 PD168393. PD168393 suggesting mainly due EGFR lactate. Also, dehydrogenase A mRNA, protein expression, are downregulated when inhibited. Thus, constitutive activation seems responsible cells.