Genetic instability and the acquisition of metastatic ability by rat mammary cancer cells following v-H-ras oncogene transfection

Tomohiko Ichikawa, Natasha Kyprianou, John Tod Isaacs

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-ros 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 <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 <0.05). All four Neo/Ras transfectants that were highly metastatic had structural aberrations involving a gain in chromsome 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 significant (P <0.05). These results demon-strate 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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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Genetic instability and the acquisition of metastatic ability by rat mammary cancer cells following v-H-ras oncogene transfection. / Ichikawa, Tomohiko; Kyprianou, Natasha; Isaacs, John Tod.

In: Cancer Research, Vol. 50, No. 19, 01.10.1990, p. 6349-6357.

Research output: Contribution to journalArticle