ZIP restores estrogen receptor expression and response to Tamoxifen in estrogen receptor negative tumors

• ZIP expression was higher in primary breast tumor cells than in progressed cells.
• ZIP restored Tamoxifen sensitivity in ER-negative breast tumor cells.
• ZIP repressed EGFR expression and elevated ERalpha expression in ER-negative breast cells.
• ZIP repressed AKT-mTOR activities.
• ZIP enhanced Tamoxifen response in ER-negative breast tumor xenografts.

As a component of NURD histone deacetylase complex, ZIP serves as a tumor suppressor gene in the development of breast tumors. However, whether it takes part in chemotherapy resistance remains poorly defined. In the present study, we reported that ZIP enhanced the response to SERM chemotherapy in ER-negative cells. Overexpression of ZIP suppressed EGFR expression level and restored ERalpha protein level in cells resistant to Tamoxifen. In vivo data confirmed those in vitro findings.