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.

Our purpose was to determine whether bilateral breast cancer depends upon genetic predisposition to multiple tumors or, alternatively, represents two independent sporadic events. Biological concordance of hormone receptors and histopathology in bilateral tumors, family history of breast cancer, age at diagnosis, and survival were evaluated in 88 patients. The immunoreactivity of paired tumors from 51 patients to six different immunocytochemical markers was compared. Neither histologic patterns nor immunocytochemical reactions showed concordance between bilateral tumors. Absence of concordance (other than for estrogen receptors) and lack of associations with positive family history and early age of onset support an interpretation of independent tumor origins and does not suggest a major role for genetic determinants in the majority of cases of bilateral breast cancer.

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