Intracellular distribution of p300 and its differential recruitment to aggresomes in breast cancer.
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.
Fermento
María E
ME
Laboratorio de Biología Básica del Cáncer, Instituto de Investigaciones Bioquímicas Bahía Blanca (INIBIBB-CONICET), Camino La Carrindanga Km 7, 8000, Bahía Blanca, Argentina.
Gandini
Norberto A
NA
Lang
Cecilia A
CA
Perez
Juan E
JE
Maturi
Horacio V
HV
Curino
Alejandro C
AC
Facchinetti
María M
MM
D000230:Adenocarcinoma / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008321:Mammary Glands, Animal / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D025801:Ubiquitin; D014746:Vimentin; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D046988:Proteasome Endopeptidase Complex