c-K-ras overexpression is characteristic for metastases derived from a methylcholanthrene-induced fibrosarcoma.
We investigated the relationship between the activation of the c-myc and c-K-ras proto-oncogenes and the acquisition of metastatic potential in a methylcholanthrene-induced BALB/c fibrosarcoma. The murine fibrosarcoma GR9 was originally induced in BALB/c mice following exposure to the carcinogenic chemical 3-methylcholanthrene. To induce spontaneous metastasis, we used two tumor cell clones (B9 and G2) known to differ in their metastatic potential, local tumor growth, H-2 class I expression and sensitivity to natural killer (NK) cells. The metastatic nodes were obtained from the lung, liver and kidney. The results showed: (1) amplification of the c-myc proto-oncogene in original tumor clones as well as in all metastatic nodes; (2) mRNA overexpression without amplification of the K-ras proto-oncogene in the metastatic cells, regardless of their anatomical location; (3) no c-K-ras point mutations at codons 12 and 61, and (4) in general, a statistically significantly reduced in vitro sensitivity of metastatic tumor cells to NK cells as compared with the tumor clones used to induce them (p<0.05). These results therefore suggest that overexpressed c-K-ras mRNA is important during tumor progression, perhaps rendering metastatic tumor cells more resistant to lysis by NK cells.
Algarra
I
I
University of Jaen, Department of Health Sciences, Microbiology Unit, Jaén, Spain.
Perez
M
M
Serrano
M J
MJ
Garrido
F
F
Gaforio
J J
JJ
D000818:Animals; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology* / Q000556:secondary; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
D008748:Methylcholanthrene; D016283:Proto-Oncogene Proteins p21(ras)