Genetic instability and the acquisition of metastatic ability by rat mammary cancer cells following v-H-ras oncogene transfection.
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.
Ichikawa
T
T
Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Kyprianou
N
N
Isaacs
J T
JT
D015127:9,10-Dimethyl-1,2-benzanthracene; D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D011905:Genes, ras; D007621:Karyotyping; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D008770:Methylnitrosourea; D009362:Neoplasm Metastasis / Q000235:genetics*; D011003:Ploidies; D051381:Rats; D011919:Rats, Inbred Strains; D014162:Transfection
D004273:DNA, Neoplasm; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea