Pgr, short for progesterone receptor, is a member of the nuclear receptor superfamily. Progesterone, an important steroid hormone, exerts its physiological effects by binding to Pgr, regulating functions in both reproductive and non-reproductive tissues. Pgr is involved in several key biological processes such as female reproduction, with its signaling pathways interacting with microRNAs (miRNAs) [2]. It also has implications in embryo implantation, being essential for normal progesterone signaling during this crucial step in human reproduction [3].

In breast cancer, Pgr-KITLG signaling in HR(+) breast cancer cells drives a tumor-mast cell regulatory feedback. KITLG, transcriptionally upregulated by Pgr, elevates the production of MC-derived granulin (GRN), which attenuates TNFα-induced apoptosis in breast cancer cells. Disrupting this signaling enhances the sensitivity of HR(+) breast cancer cells to MC-induced apoptosis [1]. In endometriosis, ARID1A and Pgr proteins interact in the endometrium, and ARID1A levels positively correlate with Pgr levels, which may contribute to understanding endometrial receptivity and progesterone resistance in this disorder [4].

In summary, Pgr is crucial for female reproduction, embryo implantation, and has implications in breast cancer and endometriosis. Gene knockout or conditional knockout mouse models, like the Pgr-Cre mouse line used to study embryo implantation, have significantly contributed to revealing the role of Pgr in these biological processes and disease conditions, deepening our understanding of related molecular mechanisms and potentially guiding precision medicine development [1,3,4].

References:

1. Yang, Zeyu, Chen, Hongdan, Yin, Supeng, Shi, Chunmeng, Zhang, Fan. 2024. PGR-KITLG signaling drives a tumor-mast cell regulatory feedback to modulate apoptosis of breast cancer cells. In Cancer letters, 589, 216795. doi:10.1016/j.canlet.2024.216795. https://pubmed.ncbi.nlm.nih.gov/38556106/

2. Chen, Long, Zhang, Bao-yun, Feng, Guang-de, Chu, Ming-xing, Wang, Ping-qing. . [The mechanism of miRNA-mediated PGR signaling pathway in regulating female reproduction]. In Yi chuan = Hereditas, 38, 40-51. doi:10.16288/j.yczz.15-293. https://pubmed.ncbi.nlm.nih.gov/26787522/

3. Zheng, Zhan-Hong, Zhang, Guo-Le, Jiang, Run-Fu, Yang, Shi-Hua, Liu, Ji-Long. 2023. METTL3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of progesterone receptor. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2214684120. doi:10.1073/pnas.2214684120. https://pubmed.ncbi.nlm.nih.gov/36693099/

4. Kim, Hong Im, Kim, Tae Hoon, Yoo, Jung-Yoon, Ku, Bon Jeong, Jeong, Jae-Wook. 2021. ARID1A and PGR proteins interact in the endometrium and reveal a positive correlation in endometriosis. In Biochemical and biophysical research communications, 550, 151-157. doi:10.1016/j.bbrc.2021.02.144. https://pubmed.ncbi.nlm.nih.gov/33706098/