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  • Title: Genetic instability and the acquisition of metastatic ability by rat mammary cancer cells following v-H-ras oncogene transfection.
    Author: Ichikawa T, Kyprianou N, Isaacs JT.
    Journal: Cancer Res; 1990 Oct 01; 50(19):6349-57. PubMed ID: 2119253.
    Abstract:
    When nonmetastatic dimethylbenzanthracene-induced rat mammary cancer cells (RMC1) were transfected with a control plasmid containing the neomycin resistance gene (i.e., Neo/Only), none of the five clonal Neo/Only transfectants isolated and characterized was metastatic, only one of five had a single structural chromosomal abnormality, and only one of five had a single numerical chromosomal change not present in the untransfected parental RMC1 cells. In contrast, when RMC1 cells were transfected with a plasmid containing both the neo resistance and mutated v-H-ras oncogene (i.e., Neo/Ras), four of nine clonal Neo/Ras transfectants isolated and characterized were highly metastatic, and all nine had multiple structural and/or additional numerical chromosomal abnormalities. The frequency of transfectants which had structural and/or additional numerical chromosomal changes in Neo/Ras transfectants was significantly higher than that in Neo/Only transfectants (P less than 0.05). In addition, seven of nine Neo/Ras transfectants had structural abnormalities in chromosome 1, whereas none of five Neo/Only transfectants had such abnormalities (P less than 0.05). All four Neo/Ras transfectants that were highly metastatic had structural aberrations involving a gain in chromosome 4. In contrast, none of the three Neo/Ras transfectants which were of low metastatic ability had a similar aberration involving chromosome 4. Correlation between a gain in chromosome 4 and a gain of high metastatic ability was significantly (P less than 0.05). These results demonstrate that, when RMC1 cells are transfected with v-H-ras, transfectants expressing the mutated v-H-ras p21 become genetically unstable and undergo chromosomal changes. These studies suggest that, if the appropriate chromosomal changes occur, these v-H-ras transfectants acquire high metastatic ability.
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