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

Abstract：

: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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Sang M,Li Y,Ozaki T,Ono S,Ando K,Yamamoto H,Koda T,Geng C,Nakagawara A

doi

10.1016/j.bbrc.2006.06.079

subject

Has Abstract

pub_date

2006-08-18 00:00:00

pages

327-33

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)01401-X

journal_volume

347

pub_type

杂志文章

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