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Research Article

Targeting ETV4 in ER-positive breast cancer: Anti-tumor effects of MEK1/2 inhibition with trametinib
Dasom Kim1
,
Ji Won Kim1*
1Department of Pharmacy, Jeju National University, Jeju 63243, Republic of Korea
*Corresponding Author
29 August 2025. pp. 35-42
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Abstract

Estrogen receptor (ER)-positive (ER+) breast cancer is one of the most common subtypes of breast cancer, but resistance to current therapies remains a significant clinical challenge. ETV4, a member of the ETS transcription factor family, has been implicated in promoting tumor progression and therapy resistance. In this study, we investigated the effects of the MEK1/2 inhibitor trametinib on ETV4 expression and its downstream anti-cancer effects in ER+ breast cancer cells. Notably, trametinib, as an FDA-approved MEK1/2 inhibitor, has demonstrated clinical efficacy in various cancer subtypes. In the MCF7 cell line, an ER+ breast cancer model, trametinib treatment significantly reduced ETV4 transcription, which was accompanied by decreased cell proliferation, 3D spheroids growth. Additionally, the level of ETV4 was elevated as MCF-7 cells acquired resistance to tamoxifen, correlating with an increased rate of cell proliferation. This suggests that the upregulation of ETV4 protein may represent a key molecular mechanism driving enhanced cell growth associated with tamoxifen resistance. Mechanistically, trametinib-mediated ETV4 suppression was associated with the downregulation of key oncogenic pathway, including mitogen-activated protein kinase (MAPK) signaling. Our data highlights the critical role of ETV4 in ER+ breast cancer progression and suggests that targeting ETV4 via MEK inhibition with trametinib may serve as a promising therapeutic strategy.

Keywords
Breast cancer
MEK1/2 inhibitor
Trametinib
ETV4
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Information
  • Publisher :Jeju Journal of Island Sciences
  • Publisher(Ko) :제주섬과학회지
  • Journal Title :Jeju Journal of Island Sciences
  • Journal Title(Ko) :제주섬과학회지
  • Volume : 2
  • No :2
  • Pages :35-42
  • Received Date : 2024-04-18
  • Revised Date : 2025-08-20
  • Accepted Date : 2025-08-20
  • DOI :https://doi.org/10.23264/JJIS.2025.2.2.035
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