Abstract
Estrogen receptor alpha positive (ER+) of breast cancer could develop resistance to antiestrogens including Tamoxifen. Our previous study showed that the E3 ubiquitin ligase HRD1 played an important role in anti-breast cancer. However, its role in chemotherapy resistance hasn't been reported. In this study, we found that HRD1 expression was downregulated in Tamoxifen-resistant breast cancer cell line MCF7/Tam compared to the Tamoxifen sensitive cell line MCF7. Moreover, S100A8 is the direct target of HRD1 by proteome analysis. Our data showed that HRD1 decreased the protein level of S100A8 through ubiquitination while HRD1 was regulated by acetylation of histone. More importantly, HRD1 knockdown significantly increased the cell survival of MCF7 cells to the Tamoxifen treatment. HRD1 overexpression sensitized MCF7/Tam cells to the Tamoxifen treatment in vitro and in vivo. In conclusion, the decrease of HRD1 expression contributed to Tamoxifen resistance in breast cancer.
Highlights
The breast cancer is one of the most common cancers among the women in the whole world
We found that HRD1 expression was downregulated in Tamoxifen-resistant breast cancer cell line MCF7/ Tam compared to the Tamoxifen sensitive cell line MCF7
We have found the E3 ubiquitin ligase of HRD1 was involved in the Tamoxifen resistance of breast cancer and could be the new target for the treatment of ER+ breast cancer in the clinical
Summary
The breast cancer is one of the most common cancers among the women in the whole world. 70% are estrogen receptor alpha positive (ER+) breast cancer. In the clinical, the major therapy is the Tamoxifen or other aromatase inhibitors in order to block estrogen receptor and inhibit the activation of downstream genes. About 50% of ER+ breast tumors develop resistance to these drugs including Tamoxifen [1, 2]. Contributes to the deaths of breast cancer patients. The understanding of the molecular mechanisms underlying the chemistry-drug resistance of breast cancer remains incomplete
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
