p73-dependent induction of 14-3-3sigma increases the chemo-sensitivity of drug-resistant human breast cancers

It has been well documented that tumor suppressor p53 is mutated in about 50% of all human tumors. p53 status might be one of the critical determinants for the chemo-sensitivity of human tumors. In the present study, we have found that p53 family member p73 as well as 14-3-3sigma is down-regulated i...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-08, Vol.347 (1), p.327-333
Main Authors: Sang, Meixiang, Li, Yuanyuan, Ozaki, Toshinori, Ono, Sayaka, Ando, Kiyohiro, Yamamoto, Hideki, Koda, Tadayuki, Geng, Cuizhi, Nakagawara, Akira
Format: Article
Language:English
Subjects:
14-3-3 Proteins
Antibiotics, Antineoplastic - administration & dosage
Biomarkers, Tumor
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Line, Tumor
Cell Survival - drug effects
DNA-Binding Proteins - metabolism
Dose-Response Relationship, Drug
Doxorubicin - administration & dosage
Drug Resistance, Neoplasm
Exonucleases
Exoribonucleases
Gene Expression Regulation, Neoplastic - drug effects
Genes, Tumor Suppressor
Humans
Neoplasm Proteins
Nuclear Proteins - metabolism
Tumor Protein p73
Tumor Suppressor Protein p53 - metabolism
Tumor Suppressor Proteins
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Summary:It has been well documented that tumor suppressor p53 is mutated in about 50% of all human tumors. p53 status might be one of the critical determinants for the chemo-sensitivity of human tumors. In the present study, we have found that p53 family member p73 as well as 14-3-3sigma is down-regulated in response to adriamycin (ADR) in ADR-resistant human breast cancer-derived MBA-MD-436 cells which carry p53 mutation. Like p53, 14-3-3sigma was transactivated by p73 and, in turn, stabilized p73. Luciferase reporter analysis and colony formation assays demonstrated that 14-3-3sigma has an ability to enhance the p73-mediated transcriptional activity as well as its pro-apoptotic function. Furthermore, enforced expression of 14-3-3sigma increased the ADR sensitivity of MBA-MD-436 cells. Taken together, our present results strongly suggest that p73-dependent induction of 14-3-3sigma plays an important role in the regulation of chemo-sensitivity of breast cancers bearing p53 mutation.
ISSN:0006-291X