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.
Spontaneously immortalized human mammary epithelial cells MCF-10A were transfected with an activated c-Ha-ras oncogene. Transfected cells (MCF-10T) acquire a malignant phenotype, as already reported. Studies of 125I-2'-deoxyuridine incorporation in cultures given graded doses of hydrocortisone (HC), cholera toxin (CT), epidermal growth factor (EGF), and transforming growth factor alpha (TGF-alpha) showed that though MCF-10T had become almost independent on exogenous EGF and TGF-alpha, 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-I 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-alpha failed to modulate EGF-R. In contrast, HC strongly stimulated the expression of EGF-R while depressing MHC class-I molecules. Thus, it appears that in vivo HC may co-operate with TGF-alpha 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.
Basolo
F
F
Institute of Pathological Anatomy, University of Pisa, Italy.
Serra
C
C
Ciardiello
F
F
Fiore
L
L
Russo
J
J
Campani
D
D
Dolei
A
A
Squartini
F
F
Toniolo
A
A
D000943:Antigens, Differentiation / Q000032:analysis*; D001940:Breast; D002461:Cell Line, Transformed / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000032:analysis; D011905:Genes, ras; D006680:HLA Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D000943:Antigens, Differentiation; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D006854:Hydrocortisone