Tumor and growth suppression of breast cancer cells by chromosome 17-associated functions.
Losses of functions from chromosome 17 are the most frequent genetic abnormalities in human breast cancer. To assess the biological role of chromosome 17 in the development of breast cancer, we transferred a normal human chromosome 17 to two breast cancer cell lines. No viable clone 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 transferred 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 phenotype. The p53 protein most likely was responsible for the selective loss of the short arm of the chromosome. Both cell lines have no wild-type 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 wild-type p53 produced only clones with rearrangements of the transfected TP53 complementary DNA. Thus, nonregulated expression of the p53 protein driven by the strong cytomegalovirus promoter may have triggered a rapid process of cell death. Stable expression of a mutant p53 in MCF-7 cells proved that nuclear localization of the protein was possible; however, no progression toward an estrogen-independent tumorigenic phenotype 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 of breast neoplasms.
Negrini
M
M
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Sabbioni
S
S
Haldar
S
S
Possati
L
L
Castagnoli
A
A
Corallini
A
A
Barbanti-Brodano
G
G
Croce
C M
CM
D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division; D002460:Cell Line; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D017931:DNA Primers; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D016158:Genes, p53; D006801:Humans; D006822:Hybrid Cells; D017354:Point Mutation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D017931:DNA Primers; D016159:Tumor Suppressor Protein p53