Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression

Journal Article · Sat Aug 01 04:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.15.5143· OSTI ID:5172528

Radinsky, R; Kraemer, P M; Raines, M A; Kung, H J; Culp, L A

Analyses of the cellular and viral Kirsten ras genes (c-Ki-ras and v-Ki-ras, respectively) during malignant tumor progression were performed by using Kirsten murine sarcoma virus-transformed BALB/c 3T3 cells that harbor a replication-defective provirus. After injection into athymic nude mice by four different routes, primary tumors and secondary lung metastases were isolated, adapted to in vitro growth, and analyzed for DNA levels and mRNA expression of both genes for comparison with the originally injected transformed cells and untransformed 3T3 cells. For all tumors (primary or secondary), the v-Ki-ras gene was amplified and v-Ki-ras mRNA expression was highly elevated above that observed in the original transformed cell population. In two of five lung metastases from the i.v. and footpad injection routes, rearranged Ki-ras DNA sequences were observed. Micrometastases from the s.c. route of injection did not display these alterations. Injection of footpad lung tumor cells with rearrangements into a second group of animals led to multiple lung metastases with even further rearrangements correlating with more effective lung colonization/growth ability. However, reinjection of an i.v. lung tumor with rearranged Ki-ras led to no further rearrangements in the lung microfoci tumors isolated > 40 days after injection. These data suggest (i) the significance of amplification and elevated expression of v-Ki-ras in tumor formation, (ii) correlation of this amplification with more effective tumor progression, and (iii) the selective advantage that cells with Ki-ras DNA sequence additions have in the formation of overt lung tumors.

• Research Organization: Case Western Reserve Univ., Cleveland, OH (USA)
• OSTI ID: 5172528
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:15; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
BODY
CARCINOGENESIS
CONNECTIVE TISSUE CELLS
DNA
DNA SEQUENCING
FIBROBLASTS
GENE AMPLIFICATION
GENES
GENOTYPE
LUNGS
MAMMALS
MESSENGER-RNA
METASTASES
MICE
NUCLEIC ACIDS
ONCOGENES
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
RESPIRATORY SYSTEM
RNA
RODENTS
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES