Clonal variation of tumorigenic potential in v-Ha-ras-transformed human bronchial epithelial cells: relationship to ras oncogene expression and CAD gene amplification.
Infection of an SV40 large-T antigen-"immortalized" human bronchial epithelial cell line with a Zip-v-Ha-ras retroviral vector resulted in a mass culture that was tumorigenic in athymic nude mice. A tumor cell line derived from passage of the mass culture in vivo, however, exhibited increased tumorigenicity and v-Ha-ras expression. To examine and compare the molecular events involving the ras oncogene during cell transformation in vitro and subsequent tumor formation in vivo, clonal cell populations were isolated from the v-Ha-ras-transformed mass culture. While the clonal cell lines exhibited diverse tumorigenic profiles, these differences did not correlate with v-Ha-ras expression. However, the expression of the activated ras gene, while not necessary for growth in vitro, did appear to be associated with a selective growth advantage in vivo. In addition, the modulation of gene amplification ability in these cells was not associated with the induction of tumorigenicity or v-Ha-ras expression.
Forrester
K
K
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Kispert
J
J
Sanchez
J H
JH
Gerwin
B I
BI
Tlsty
T D
TD
Harris
C C
CC
D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000235:genetics*; D001980:Bronchi / Q000166:cytology; D001984:Bronchial Neoplasms / Q000235:genetics*; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000235:genetics*; D002472:Cell Transformation, Viral; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000235:genetics; D004080:Dihydroorotase / Q000235:genetics*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009097:Multienzyme Complexes / Q000235:genetics*; D009368:Neoplasm Transplantation; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured
C033626:CAD trifunctional enzyme; D004273:DNA, Neoplasm; D009097:Multienzyme Complexes; D012334:RNA, Neoplasm; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)