Nogo-B receptor increases the resistance of estrogen receptor positive breast cancer to paclitaxel.

ABSTRACT: Intrinsic or acquired chemoresistance is a hurdle in oncology. Only 7%-16% of estrogen receptor ? (ER?) 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 ER? positive breast cancer patients to attenuate paclitaxel resistance. NgBR knockdown enhanced paclitaxel-induced cell apoptosis by modulating expression of p53 and survivin in ER? positive breast cancer cells via NgBR-mediated PI3K/Akt and MAPK/ERK signaling pathways. NgBR knockdown attenuated either 17?-estradiol or epidermal growth factor stimulated phosphorylation of ER? at Serine 118 residue. The ChIP-PCR assay further demonstrated that NgBR knockdown decreased ER? binding to the estrogen response element (ERE) of the ER? 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 ER? positive breast cancer cell resistance to paclitaxel. Findings from this study implicate a novel therapeutic target for treating ER? positive breast cancer in neo-adjuvant/adjuvant chemotherapy.

SUBMITTER: Jin Y 

PROVIDER: S-EPMC5821135 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature