Abstract 3978: The growth inhibitory effect of MDV3100 on hormone receptor-positive, HER2-negative breast cancer cell lines with low DYRK2 expression

Abstract

Abstract Introduction: Tumor progression is the main cause of death in patients with breast cancer. Accumulating evidence suggests that dual-specificity tyrosine-regulated kinase 2 (DYRK2) functions as a tumor suppressor by regulating cell survival, differentiation, proliferation and apoptosis. Recently, we reported for the first time that DYRK2 inhibits breast cancer stem cells and tumor cell proliferation through transcriptional downregulation of KLF4 and CDK14, respectively.Our previous study showed that Androgen receptor (AR) was a DYRK2-dependent transcriptional activator. In this context, we hypothesized that MDV3100, an inhibitor of AR, may be effective for breast cancer with low DYRK2 expression. Methods: We established stable DYRK2-depleted cells. MCF-7 cells, hormone receptor-positive, HER2-negative breast cancer cell line, were transfected with pSuper-puro vector (pSuper control) or pSuper-puro DYRK2 shRNAs (shDYRK2) along with puromycin to isolate stable cell lines.These manipulated cells were compared with the control cells by various assays. We analyzed the activity of AR by Androgen receptor reporter assay. MTS assays were used to assess growth inhibition after treatment with MDV3100. Results: Androgen receptor reporter assay showed that knocking down DYRK2 induced AR transcription activity in MCF-7 cells.In MCF-7 DYRK2-depleted cells, MTS assays revealed that the treatment by MDV3100 was more effective than that in MCF-7 control cells. Conclusion: These findings demonstrate that reduced DYRK2 expression in hormone receptor-positive, HER2-negative breast cancer increases the activity of AR and significantly inhibits the growth by treatment with MDV3100. Citation Format: Yoshimi Imawari, Rei Mimoto, Kiyotsugu Yoshida. The growth inhibitory effect of MDV3100 on hormone receptor-positive, HER2-negative breast cancer cell lines with low DYRK2 expression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3978.