Regulation of surface‐differentiation molecules by epidermal growth factor, transforming growth factor alpha, and hydrocortisone in human mammary epithelial cells transformed by an activated c‐Ha‐ras proto‐oncogene

Abstract

Spontaneously immortalized human mammary epithelial cells MCF‐IOA were transfected with an activated c‐Ha‐ras oncogene. Transfected cells (MCF‐IOT) acquire a malignant pheno‐type, as already reported. Studies of l‐2′‐deoxyuridine incorporation in cultures given graded doses of hydrocortisone (HC), cholera toxin (CT), epidermal growth factor (EGF), and transforming growth factor alpha (TGF‐α) showed that though MCF‐IOT had become almost independent on exogenous EGF and TGF‐α, they continued to respond to the synergistic effect of HC and CT plus EGF. Both lines were phenotypically characterized with an immunoradiometric assay in live cells. Expression of MHC class‐I molecules, human milk‐fat‐globule‐1 antigen, and EGF receptor was reduced in ras‐transfected cells, although other differentiation markers were unchanged. Exogenous EGF down‐regulated the expression of functional EGF‐R, selectively in transformed cells. TGF‐α failed to modulate EGF‐R. In contrast, HC strongly stimulated the expression of EGF‐R while depressing MHC class‐l molecules. Thus, it appears that in vivo HC may co‐operate with TGF‐α and EGF in promoting the growth of transformed mammary cells. This hormone might also favor the escape from immune surveillance by reducing the expression of surface differentiation markers.