Open Access

ARTICLE

Inhibitory Effect of Progesterone on Breast Cancer Progression and Migration via the Regulation of Epithelial-Mesenchymal Transition

So-Ye Jeon^1,#, Zeeshan Ahmad Bhutta^1,#, Hong Kyu Lee², Kyung-Chul Choi^1,*

1 Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea
2 Department of Companion Animal Health, College of Biomedical Science & Health, Inje University, Gimhae, Republic of Korea

* Corresponding Author: Kyung-Chul Choi. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Breast Cancer Biomarkers and Drug Targets Discoveries Towards a More Personalized Treatment Setting)

Oncology Research 2026, 34(4), 18 https://doi.org/10.32604/or.2026.071328

Received 05 August 2025; Accepted 26 December 2025; Issue published 23 March 2026

Abstract

Objectives: Progesterone (P4) is believed to inhibit breast cancer growth, but its role in counteracting estrogen (E2)-driven progression remains unclear. This study aimed to investigate the inhibitory effect of P4 on E2-induced cell proliferation, migration, and invasion in Estrogen receptor (ER)+/progesterone receptor (PR)+ breast cancer cells by examining its regulatory role in the epithelial-mesenchymal transition (EMT). Methods: ER and PR-positive MCF-7 clonal variant (MCF-7 CV) breast cancer cells were treated with E2 and co-treated with various concentrations of P4. The effects on cell proliferation, migration, and invasion were assessed. The expression of key EMT markers (E-cadherin, N-cadherin, vimentin), transcription factors (Snail, Slug), and apoptosis-related genes (p53, B-cell lymphoma 2 [BCL-2], BCL2-associated X [BAX]) were analyzed. Results: P4 significantly inhibited E2-induced cell proliferation in a dose-dependent manner. In the presence of E2, P4 treatment reversed EMT characteristics by increasing E-cadherin while decreasing N-cadherin, vimentin, Snail, and Slug. Consequently, P4 inhibited E2-stimulated cell migration and invasion. Furthermore, P4 treatment promoted apoptosis by upregulating BAX and p53 and downregulating BCL-2. Conclusion: Progesterone can counteract estrogen-driven breast cancer progression in ER+/PR+ cells by inhibiting proliferation, reversing the EMT process, and inducing apoptosis. These findings provide mechanistic insight into the protective role of PR signaling in breast cancer.

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