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
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.