Transformation of Human Breast Epithelial Cells by c‐Ha‐ras Oncogene

Abstract

To determine whether the c‐Ha‐ras oncogene plays a role in the initiation of mammary carcinogenesis, an immortalized human breast epithelial cell line, MCF‐10A, was transfected with the plasmid vector pHo6T1 containing the T24 Ha‐ras oncogene and the aminoglycoside phosphotransferase gene, which confers resistance to geneticin. Transfected cells exhibited an altered pattern of growth and tridimensional morphology in collagen gel. They also exhibited anchorage‐independent growth and loss of requirement for hormones and epidermal growth factor; in addition, they expressed invasiveness and increased collagenolytic activity in an in vitro system and became tumorigenic in irradiated nude mice, all properties indicative of malignant transformation. Transformed cells contained the mutated c‐Ha‐ras oncogene and expressed the p21 mutated protein. These data indicate that the c‐Ha‐ras oncogene is capable of inducing malignant phenotypes in immortalized human breast epithelial cells.