Activated N-ras oncogene and N-ras proto-oncogene act through the same pathway for in vivo tumorigenesis.
We compared the tumorigenic effects of the N-ras oncogene and the N-ras proto-oncogene in lymphoid and mammary tissues in an in vivo model. For this purpose, we generated transgenic mice with high levels of N-ras oncogene or N-ras proto-oncogene expression, driven by the complete mouse mammary tumor virus LTR (MMTV-LTR) (MMTV/N-rasT and MMTV/N-rasN constructs) and transgenic mice with low levels of N-ras oncogene or N-ras proto-oncogene expression, driven by a truncated MMTV-LTR (TMTV/N-rasT and TMTV/N-rasN constructs). We show that both, the N-ras proto-oncogene and the N-ras oncogene with a C:G-->A:T mutation at codon 61, lead to identical tumor types: lymphoblastic T-cell lymphomas, cleaved B-cell lymphomas and poorly differentiated mammary carcinomas. Nevertheless, there were quantitative differences in tumor incidence and latency and in transgene expression among N-ras oncogene and N-ras proto-oncogene transgenics. Despite these differences in tumor kinetics, the predisposition to identical tumor types is in agreement with the idea that the N-ras oncogene and the N-ras proto-oncogene act through the same pathway for in vivo tumorigenesis in B-cells, T-cells or mammary epithelial cells.
Mangues
R
R
Department of Pathology, New York University Medical Center, NY 10016, USA.
Symmans
W F
WF
Lu
S
S
Schwartz
S
S
Pellicer
A
A
D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D015994:Incidence; D016393:Lymphoma, B-Cell / Q000453:epidemiology / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000453:epidemiology / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000453:epidemiology / Q000235:genetics*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics
D018631:ras Proteins