Endocrine Abstracts

Breast cancers that are estrogen receptor (ER)/progesterone receptor (PR)-positive are more likely to respond to hormone-related treatments than tumors that are ER/PR-negative. The present study investigated the effect of progesterone (P4) on 17β-estradiol (E2)-induced cell proliferation, apoptosis, EMT, and migratory and invasive features of MCF-7 clonal varient (CV) breast cancer cells that are ER/PR-positive. Preferentially, E2 was verified to induce breast cancer progression by stimulating cell proliferation, EMT, and migration of MCF-7 CV breast cancer cells. On the other hand, P4 reduced E2-induced MCF-7 CV cell proliferation by down-regulating the protein expression of cyclin D1 and E1 and induced apoptosis of MCF-7 CV cells by up-regulating Bax and p53 and by down-regulating Bcl-2. Also, P4 appeared to inhibit E2-induced EMT process by increasing mRNA and protein expression of E-cadherin, a crucial epithelial marker, as well as by reducing the expression of mesenchymal markers such as N-cadherin and vimentin and EMT-associated transcription factors such as snail and slug. Eventually, E2-induced migration and invasion ability of MCF-7 CV cells and the protein expression of proteolytic enzymes such as MMP-9 and cathepsin B were reduced by P4 treatment. Co-treatment of RU486, a PR inhibitor, restored the inhibited cellular migration and invasion and the reduced expression of proteases by P4 to the control levels, suggesting the involvement of PR in P4-induced inhibition on migration and invasion of MCF-7 CV cells. Taken together, P4 treatment may be suggested as an effective tool for suppression of human breast cancer progression and metastasis. (This work was supported by a grant from the Next-Generation BioGreen 21 Program (no. PJ011355-2015), Rural Development Administration, Republic of Korea.)

Keywords: Progesterone; breast cancer cells; epithelial-mesenchymal transition; metastasis; migration.