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Proteomic identification of E 6 AP as a molecular target of tamoxifen in MCF 7 cells
Author(s) -
Lochab Savita,
Pal Pooja,
Kanaujiya Jitendra K.,
Tripathi Shashi B.,
Kapoor Isha,
Bhatt Madan L. B.,
Sanyal Sabyasachi,
Behre Gerhard,
Trivedi Arun K.
Publication year - 2012
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201100572
Subject(s) - downregulation and upregulation , tamoxifen , cancer research , mcf 7 , breast cancer , apoptosis , estrogen receptor , chemistry , cancer , biology , medicine , biochemistry , human breast , gene
Tamoxifen ( T am) is most widely used selective estrogen receptor modulator ( SERM ) for treatment of hormone‐responsive breast cancer. Despite being regularly used in clinical therapy for breast cancer since 1971, the mechanism of T am action remains largely unclear. In order to gain insights into T am‐mediated antibreast cancer actions, we applied 2DE and MS based proteomics approach to identify target proteins of T am. We identified E 6‐associated protein, i.e. E 6 AP ( UBE 3 A ) among others to be regulated by T am that otherwise is upregulated in breast tumors. We confirmed our 2DE finding by immunoblotting and further show that T am leads to inhibition of E 6 AP expression presumably by promoting its autoubiquitination, which is coupled with nuclear export and subsequent proteasome‐mediated degradation. Furthermore, we show that T am‐ and si E 6 AP ‐mediated inhibition of E 6 AP leads to enhanced G 0– G 1 growth arrest and apoptosis, which is also evident from significant upregulation of cytochrome‐c, B ax, p21, and PARP cleavage. Taken together, our data suggest that, T am‐targeted E 6 AP inhibition is in fact required for T am‐mediated antibreast cancer actions. Thus, E 6 AP may be a therapeutic target in breast cancer.