Intracellular distribution of p300 and its differential recruitment to aggresomes in breast cancer.
Exp Mol Pathol
; 88(2): 256-64, 2010 Apr.
Article
em En
| MEDLINE
| ID: mdl-20097195
It has been recently suggested that p300 cytoplasmic redistribution and degradation are important for controlling the availability and activity of the protein as a transcriptional coactivator. As a step towards determining the functional relevance of p300 intracellular redistribution in mammary cancer, we aimed at studying p300 localization in two different animal models of mammary carcinoma as well as in human primary breast carcinoma samples. Analysis of p300 protein levels showed stronger expression in tumor epithelia than in normal mammary gland. Cytoplasmic localization of p300 was observed in malignant cells. Furthermore, cytoplasmic p300 was found in tumor epithelia whereas nuclear localization was observed in normal mammary glands in both animal models and in non-malignant adjacent areas of human breast cancer specimens. Interestingly, proteasomal inhibition induced p300 redistribution to perinuclear inclusion bodies in tumor but not in normal mammary gland-derived cells. These inclusions were confirmed to be aggresomes by doing immunofluorescence for ubiquitin, vimentin and 20S proteasomal subunit. Taken together, these findings show that both the localization of p300 and the recruitment to aggresomes differ between mammary tumors and normal mammary glands, and suggest that the formation of these inclusions could be a potential target for therapeutic intervention.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mama
/
Neoplasias da Mama
/
Proteína p300 Associada a E1A
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Exp Mol Pathol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Argentina
País de publicação:
Holanda