Transformation of human breast epithelial cells by c-Ha-ras oncogene.
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.
Basolo
F
F
Michigan Cancer Foundation, Detroit 48201.
Elliott
J
J
Tait
L
L
Chen
X Q
XQ
Maloney
T
T
Russo
I H
IH
Pauley
R
R
Momiki
S
S
Caamano
J
J
Klein-Szanto
A J
AJ
D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D007621:Karyotyping; D014162:Transfection; D014410:Tumor Stem Cell Assay