Progesterone receptor B induces autophagy antagonizing the phosphatidylinositol-3 kinase PI3K/AKT pathway in breast cancer cell lines
F. De Amicis, C. Guido, M. Santoro, P. Avena, I. Perrotta, M. Panno, S. Panza, R. Bruno & S. Aquila
Progesterone (PRG) deficiency has been linked to an increased risk of cancer, while normal levels of PRG in the body actually help protect you against some forms of cancer. The tumor suppressor role of this steroid was envisaged, however the mechanism through which this occurs was not clearly established. The effects of progesterone act via the progesterone receptor (PR) of which two isoforms, called A (PR-A) and B (PR-B) were discovered. Herein, we present a novel finding since PRG through PR-B induces of cell death by autophagy in breast cancer cells. The link between autophagy and cancer appears to be complex and multifaceted. Of importance is the understanding of the circumstances under which autophagy promotes either cell death or cell survival in the context of tumorigenesis, as this may have implications in cancer therapy. Analysis of different autophagy-related markers such as AMPK, AKT, mTOR, PI3III, Beclin 1, AMBRA and UVRAG indicated for the first time the ability of OHPg/PR-B to induce their expression. The monitoring of autophagic process, assessed by either biochemical (MDC) and ultrastructural methods (TEM), confirmed the molecular data. In the present study we report that PRG, through the PR-B isoform, produces a significant inhibition of MCF-7 breast cancer cell survival by autophagy. These data underscore a novel mechanism through which PRG/PR-B exerts its beneficial effects on breast cancer, sustaining that PRG/PR signaling may be considered as useful pharmacological tool to be exploited for innovative adjuvant strategies in breast cancer treatment.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.