Aberrant PTEN expression in response to progesterone reduces endometriotic stromal cell apoptosis. Issue 1 (January 2017)

• Record Type: Journal Article
• Authors: Choi, JongYeob; Jo, MinWha; Lee, EunYoung; Hwang, Seongsoo; Choi, DooSeok
• Is Part Of: Reproduction. Volume 153:Issue 1(2017)
• Page Start: 11
• Page End: 21
• Publication Date: 2017-01
• Subjects: Reproduction -- Periodicals; Reproduction -- Molecular aspects -- Periodicals; Reproduction -- Immunological aspects -- Periodicals; Reproduction -- Endocrine aspects -- Periodicals; Fertility -- Periodicals; Human reproduction -- Periodicals; 571.805
• DOI: 10.1530/REP-16-0322
• Languages: English
• ISSNs: 1470-1626

Abstract

Abstract : In some human cancer cells, PTEN (phosphatase and tensin homolog deleted on chromosome 10) is known to regulate autophagy induction positively through the inhibition of PI3K/AKT pathway, leading to the activation of mTOR, a major negative regulator of autophagy. Recent studies reported that PTEN expression is abnormally decreased in endometriotic lesions. In endometriosis, abnormal PTEN expression may contribute to the alteration of endometrial cell autophagy, which may affect apoptosis because endometrial cell autophagy is directly involved in the regulation of apoptosis. To test this hypothesis, we evaluated the involvement of PTEN in the regulation of autophagy induction in human normal endometrial stromal cells (NESCs). In addition, we sought to determine whether aberrant PTEN expression in endometriotic cyst stromal cells (ECSCs) is associated with autophagy dysregulation, and a subsequent decrease in apoptosis. Our results show that PTEN expression was enhanced by progesterone treatment in NESCs. Subsequently, autophagy and apoptosis induction increased through the inhibition of AKT and mTOR activity. This progesterone-induced increase in apoptosis was reversed by the inhibition of autophagy induction using either mifepristone (progesterone receptor modulator) or PTEN inhibitor. In contrast, progesterone had no significant effects on PTEN expression, AKT, mTOR activity, autophagy or apoptosis in ECSCs. Furthermore, in contrast to normal eutopic endometrium, endometriotic tissues have constant PTEN expression, autophagy and apoptosis throughout the menstrual cycle. In conclusion, our results suggest abnormal PTEN expression in response to progesterone was observed in ECSCs, which led to the dysregulation of autophagy induction via AKT/mTOR signalling and a subsequent decrease in apoptosis.