TUMOR AND GROWTH SUPPRESSION OF BREAST-CANCER CELLS BY CHROMOSOME-17-ASSOCIATED FUNCTIONS

Citation
M. Negrini et al., TUMOR AND GROWTH SUPPRESSION OF BREAST-CANCER CELLS BY CHROMOSOME-17-ASSOCIATED FUNCTIONS, Cancer research, 54(7), 1994, pp. 1818-1824
Citations number
48
Categorie Soggetti
Oncology
Journal title
ISSN journal
00085472
Volume
54
Issue
7
Year of publication
1994
Pages
1818 - 1824
Database
ISI
SICI code
0008-5472(1994)54:7<1818:TAGSOB>2.0.ZU;2-2
Abstract
Losses of functions from chromosome 17 are the most frequent genetic a bnormalities in human breast cancer. To assess the biological role of chromosome 17 in the development of breast cancer, we transferred a no rmal human chromosome 17 to two breast cancer cell lines. No viable cl one maintaining an intact chromosome was obtained in either MDA-MB-231 or MCF-7. Only one MDA-231/H17 clone contained the long arm of the tr ansferred chromosome 17. Interestingly, this clone lost the ability to induce tumors in nude mice, indicating that at least one gene mapping to the long arm of chromosome 17 could suppress the tumorigenic pheno type. The p53 protein most likely was responsible for the selective lo ss of the short arm of the chromosome. Both cell lines have no wild-ty pe p53 activity. MDA-MB-231 carries a single mutant TP53 allele, while MCF-7 carries two wild-type alleles, but p53 protein is excluded from the nucleus. Transfection in both cell lines of vectors expressing wi ld-type p53 produced only clones with rearrangements of the transfecte d TP53 complementary DNA. Thus, nonregulated expression of the p53 pro tein driven by the strong cytomegalovirus promoter may have triggered a rapid process of cell death. Stable expression of a mutant p53 in MC F-7 cells proved that nuclear localization of the protein was possible ; however, no progression toward an estrogen-independent tumorigenic p henotype was induced. This work indicates that functional inactivation of the wild-type p53 protein and of the product of a gene located on 17q are essential to the development or breast neoplasms.