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Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel. Cancer Lett 2018 04 10;419:233-244

Date

01/27/2018

Pubmed ID

29373839

Pubmed Central ID

PMC5821135

DOI

10.1016/j.canlet.2018.01.054

Scopus ID

2-s2.0-85041383365   7 Citations

Abstract

Intrinsic or acquired chemoresistance is a hurdle in oncology. Only 7%-16% of estrogen receptor α (ERα) positive breast cancer cases achieve a pathological complete response (pCR) after neo-adjuvant chemotherapy. Nogo-B receptor (NgBR) is a cell surface receptor that binds farnesylated Ras and promotes Ras translocation to the plasma membrane. Here, we demonstrate NgBR as a potential therapeutic target for ERα positive breast cancer patients to attenuate paclitaxel resistance. NgBR knockdown enhanced paclitaxel-induced cell apoptosis by modulating expression of p53 and survivin in ERα positive breast cancer cells via NgBR-mediated PI3K/Akt and MAPK/ERK signaling pathways. NgBR knockdown attenuated either 17β-estradiol or epidermal growth factor stimulated phosphorylation of ERα at Serine 118 residue. The ChIP-PCR assay further demonstrated that NgBR knockdown decreased ERα binding to the estrogen response element (ERE) of the ERα target gene and increased the binding of p53 to the promoter region of survivin to attenuate survivin transcription. In summary, our data suggest that NgBR expression is essential to promoting ERα positive breast cancer cell resistance to paclitaxel. Findings from this study implicate a novel therapeutic target for treating ERα positive breast cancer in neo-adjuvant/adjuvant chemotherapy.

Author List

Jin Y, Hu W, Liu T, Rana U, Aguilera-Barrantes I, Kong A, Kumar SN, Wang B, Gao P, Wang X, Duan Y, Shi A, Song D, Yang M, Li S, Han B, Zhao G, Fan Z, Miao QR

Authors

Amanda L. Kong MD, MS Professor in the Surgery department at Medical College of Wisconsin
Suresh Kumar PhD Associate Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents, Phytogenic
Apoptosis
Breast Neoplasms
Cell Line, Tumor
Drug Resistance, Neoplasm
Estradiol
Estrogens
Female
Gene Expression Regulation, Neoplastic
Humans
MCF-7 Cells
Paclitaxel
Phosphorylation
RNA Interference
Receptors, Cell Surface
Receptors, Estrogen
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a