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Knocking down PML impairs p53 signaling transduction pathway and suppresses irradiation induced apoptosis in breast carcinoma cell MCF‐7
Author(s) -
BaoLei Tian,
ZhuZhong Mei,
Yi Song,
JunJie Qian,
Yan Dong,
Hua Liu,
Bin Liu,
GuoWei Zhao,
ZhiXian Sun
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20584
Subject(s) - apoptosis , promyelocytic leukemia protein , cancer research , mcf 7 , signal transduction , mdm2 , dna damage , biology , proteasome , cell culture , microbiology and biotechnology , chemistry , nuclear protein , cancer cell , transcription factor , gene , dna , cancer , biochemistry , genetics , human breast
The promyelocytic leukemia (PML) can selectively and dynamically recruit a number of proteins including p53 to form a sub‐nuclear multiprotein chamber named PML‐NBs. In DNA damage response, p53 is recruited into PML‐NBs and modified by phosphorylations and acetylations, which in turn potentiate its transcriptional and pro‐apoptotic activities. In contrast, in carcinoma cells, the role of PML in the irradiation induced p53‐mediated apoptosis is not precisely understood. In this study, we have used the breast carcinoma cell line, MCF‐7, and stably suppressed the expression of PML. Inhibition of PML expression had no detectable effect on the expression of endogenous p53 at the mRNA level; however, a significant decrease of p53 protein was observed. There was also an increase in the p53–MDM2 complexes, which may facilitate p53 protein degradation by the ubiquitin‐proteasome pathway, also in irradiation treated cells. The p53 transcriptional activity was attenuated both in unstressed and 10 Gy irradiation treated cells. Moreover, inhibition of PML expression in MCF‐7 cells significantly reduced p53 downstream genes, cell cycle arrest gene p21 WAF/cip−1 and pro‐apoptotic gene Bax expression, then irradiation‐induced apoptosis. These results suggest that PML is a key regulator in the irradiation activated p53 apoptotic pathway in breast carcinoma cells. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.