Transformation of human mammary epithelial cells by oncogenic retroviruses.
We have introduced viral oncogenes into human mammary epithelial cells through the use of murine retroviruses. A continuous cell line (184A1N4) derived from benzo(a)pyrene treatment of normal breast epithelial cells was used as a recipient for the ras, mos, and T-antigen oncogenes. Each of these oncogenes enabled the 184A1N4 cells to grow in a selective medium, thus demonstrating the potential utility of these cells for oncogene detection and isolation. 184A1N4 cells transformed by T-antigen were nontumorigenic in athymic mice, but v-ras transformants were weakly tumorigenic. Transformants bearing both the T-antigen and ras oncogenes were strongly tumorigenic, however. The karyotype of these double transformants shows a high degree of stability. These results demonstrate the stepwise acquisition of the fully malignant phenotype by normal human epithelial cells in vitro.
Clark
R
R
Cetus Corporation, Emeryville, California 94608.
Stampfer
M R
MR
Milley
R
R
O'Rourke
E
E
Walen
K H
KH
Kriegler
M
M
Kopplin
J
J
McCormick
F
F
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000032:analysis; D001940:Breast / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D007621:Karyotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016283:Proto-Oncogene Proteins p21(ras)
D000957:Antigens, Viral, Tumor; D011518:Proto-Oncogene Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)