CONICET | Buscador de Institutos y Recursos Humanos

The translocation between chromosomes 4 and 7, T(4;7), was observed in two different mammary carcinomas from the medroxyprogesterone acetate (MPA) mouse breast cancer model which have acquired a hormone independent (HI) phenotype (C7-2-HI and C4-HI). We had developed a cell line from the C7-2-HI tumor, the MC7-L2A cells, which retain the chromosome translocation T(4;7), and provide an easy tool to obtain metaphases. G-banding analysis showed that the breakpoint on chromosome 4 is located on the band 4E in the C7-2-HI tumor, whereas in the C4-HI tumor, it is located on the region 4C4-4D3. However, the breakpoint on chromosome 7 is located near the centromere in both tumors. Further experiments using fluorescence in situ hybridization (FISH) in MC7-L2A cells have shown that the breakpoint of the translocation involved the chromosome bands 4E2 and 7A1-A2. The aim of this project is to elucidate whether these breakpoints are involving new gene rearrangements that might participate in the acquisition of hormone independency. In this study we focused in determining if the break in chromosome 7 is located on the same band in both HI tumors. A detailed analysis in MC7-L2A cells using FISH with different DNA probes, spanning the region 7A1-7A2, showed that the breakpoint is located on chromosome 7A1 and not on band 7A2. However, a different picture was observed in metaphases obtained from C4-HI tumor cells, in which the probes corresponding to region 7A1-7B1 hybridized only to normal chromosome 7, but not to the translocation T(4;7). These results indicate that the breakpoints on chromosomes 4 and 7, although involving the same chromosomes, are located on different regions in the T(4;7) translocations, suggesting that they may be random breakpoints. Even though we could not associate this breakpoint with the hormone-independent phenotype, the identification of the sites of chromosome breaks may be relevant to understand the biology of each HI tumor.