TY  - EJOU
AU  - Jeon, So-Ye 
AU  - Bhutta, Zeeshan Ahmad 
AU  - Lee, Hong Kyu 
AU  - Choi, Kyung-Chul 

TI  - Inhibitory Effect of Progesterone on Breast Cancer Progression and Migration via the Regulation of Epithelial-Mesenchymal Transition
T2  - Oncology Research

PY  - 2026
VL  - 34
IS  - 4
SN  - 1555-3906

AB  -  <b>Objectives:</b> 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). <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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.
KW  - Progesterone; breast cancer; epithelial-mesenchymal transition

DO  - 10.32604/or.2026.071328