Effect of HIPK3 depletion in tamoxifen-resistant EGFR-overexpressing MCF7 breast cancer cells

Overexpression and activation of EGFR in breast cancer can cause resistance to antiestrogen treatmen. Using high-throughput screening, we have identified HIPK3 as a mediator of tamoxifen resistance in MCF7 breast cancer cells. HIPK3 depletion re-sensitized cells to 4-hydroxytamoxifen under EGF-stimulated conditions. In this study, we investigated the transcriptomic responses to HIPK3 depletion, together with EGF stimulation and treatment with estradiol and 4-hydroxytamoxifen. RNA-sequencing demonstrated that depletion of HIPK3 caused increased expression of genes involved in mitotic signaling, oxidative damage, endoplasmatic reticulum stress and apoptosis in EGF, estradiol and tamoxifen treated MCF7 cells.