Aim
ESE-1/Elf3 controls transformation properties in mammary epithelial cells, and is most clinically relevant in HER2+ breast cancer. Herein we showed that ESE-1 knockdown inhibits tumorigenic growth in HER2+, trastuzumab-resistant HR20 (derived from HER2+ ER+ BT474) and Pool2 (derived from HER2+ ER- SKBR3 cells) cell lines. Materials and
Conclusion
This study provides rationale to study ESE-1 as a novel mean to treat HER2+ patients who show resistance to anti-HER2 therapy.
Methods
We used cell proliferation, clonogenicity, viability, and soft agar assays to measure the effects of ESE-1 knockdown in cell lines.
Results
ESE-1 knockdown in the resistant cell lines inhibited HER2 and other downstream effectors in a cell-type specific manner, but caused down-regulation of pAkt and cyclin D1 in both sublines. In parental BT474 and SKBR3 ESE-1 silencing revealed a potent anti-proliferative effect that mimics the trastuzumab-mediated growth inhibition but did not enhance trastuzumab sensitivity in the resistant sublines.