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

Tumor and growth suppression of breast cancer cells by chromosome 17-associated functions

NEGRINI, Massimo;SABBIONI, Silvia;CORALLINI, Alfredo;BARBANTI BRODANO, Giuseppe;CROCE C. M.
1994

Abstract

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
1994
Negrini, Massimo; Sabbioni, Silvia; Haldar, S.; Possati, L.; Castagnoli, A.; Corallini, Alfredo; BARBANTI BRODANO, Giuseppe; Croce, C. M.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/462380
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 58
  • ???jsp.display-item.citation.isi??? 61
social impact