DOWN-REGULATION OF TYPE-I PROTEIN-KINASE-A BY TRANSFECTION OF HUMAN BREAST-CANCER CELLS WITH AN EPIDERMAL GROWTH-FACTOR RECEPTOR ANTISENSE EXPRESSION VECTOR

MDA-468 human breast cancer cells overexpress the EGFR and exhibit a f unctional TGF alpha-EGFR autocrine pathway. Loss of EGFR expression fo llowing stable transfection with an antisense EGFR cDNA containing pla smid down-regulates type I cAMP-dependent protein kinase (PKAI) expres sion with acquisition of cell growth resistance to the PKAI inhibitor 8-CI-cAMP. These results suggest that PKAI expression and function are controlled by a TGF alpha-EGFR autocrine pathway in human breast canc er cells overexpressing the EGFR.