scholarly journals Aberrant PTEN expression in response to progesterone reduces endometriotic stromal cell apoptosis

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. 11-21 ◽  
Author(s):  
JongYeob Choi ◽  
MinWha Jo ◽  
EunYoung Lee ◽  
Seongsoo Hwang ◽  
DooSeok Choi
Keyword(s):  
Stromal Cells ◽  
Human Cancer ◽  
Negative Regulator ◽  
Pten Expression ◽  
Endometrial Cell ◽  
Endometrial Stromal Cells ◽  
Human Cancer Cells ◽  
Subsequent Decrease ◽  
Autophagy Induction ◽  
Mtor Activity

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.

scholarly journals Involvement of autophagy induction in penta-1,2,3,4,6-O-galloyl-β-D-glucose-induced senescence-like growth arrest in human cancer cells

Autophagy ◽  
2013 ◽  
Vol 10 (2) ◽  
pp. 296-310 ◽  
Author(s):  
Yinhui Dong ◽  
Shutao Yin ◽  
Cheng Jiang ◽  
Xiaohe Luo ◽  
Xiao Guo ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Growth Arrest ◽  
Human Cancer Cells ◽  
Autophagy Induction

scholarly journals The tumor suppressor PTPRK promotes ZNRF3 internalization and is required for Wnt inhibition in the Spemann organizer

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ling-Shih Chang ◽  
Minseong Kim ◽  
Andrey Glinka ◽  
Carmen Reinhard ◽  
Christof Niehrs
Keyword(s):  
Tumor Suppressor ◽  
Wnt Signaling ◽  
Human Cancer ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Embryonic Patterning ◽  
Human Cancer Cells ◽  
Spemann Organizer ◽  
Axial Defects ◽  
Wnt Inhibitor

A hallmark of Spemann organizer function is its expression of Wnt antagonists that regulate axial embryonic patterning. Here we identify the tumor suppressor Protein tyrosine phosphatase receptor-type kappa (PTPRK), as a Wnt inhibitor in human cancer cells and in the Spemann organizer of Xenopus embryos. We show that PTPRK acts via the transmembrane E3 ubiquitin ligase ZNRF3, a negative regulator of Wnt signaling promoting Wnt receptor degradation, which is also expressed in the organizer. Deficiency of Xenopus Ptprk increases Wnt signaling, leading to reduced expression of Spemann organizer effector genes and inducing head and axial defects. We identify a '4Y' endocytic signal in ZNRF3, which PTPRK maintains unphosphorylated to promote Wnt receptor depletion. Our discovery of PTPRK as a negative regulator of Wnt receptor turnover provides a rationale for its tumor suppressive function and reveals that in PTPRK-RSPO3 recurrent cancer fusions both fusion partners, in fact, encode ZNRF3 regulators.

scholarly journals Cytotoxicity study of Shalmali extract on human endometrial stromal cells

2020 ◽  
Vol 11 (1) ◽  
pp. 1000-1003
Author(s):  
Muttevi Hyagreva Kumar ◽  
Prabhu K
Keyword(s):  
Mtt Assay ◽  
Stromal Cells ◽  
Uterine Bleeding ◽  
Antioxidant Compounds ◽  
Endometrial Cell ◽  
Endometrial Stromal Cells ◽  
Medical Practitioners ◽  
Extensive Range ◽  
Treatment Concentration

Various herbs are extensively used by the customary medical practitioners for curing numerous diseases in their day-to-day practice. Shalmali (Bombax ceiba) is a recognized plant used in the customary system for the management of various diseases. It has an extensive range of pharmacological and medicinal applications. In the current study, efforts have been made to summarize diverse aspects of scientific studies on the role of Shalmali extract on uterine bleeding. Therefore the cytotoxicity study of Shalmali extract was performed on endometrial cell lines using MTT assay. The absorbance by human endometrial stromal cells (T HESCs cells) was noted and the percentage of cell viability of T HESCs with varying treatment concentration of Shalmali extract was calculated in contrast to the standard placebo. The Shalmali extract showed cytotoxicity effect on T HESCs cells and the IC50 of the extract is 110µg/ml. To conclude that Shalmali extract showed a positive correlation was found to exist between the presence of antioxidant compounds and cytotoxicity against cells. Our results concluded that Shalmali extract could be used for the treatment of uterine bleeding.

Indirubin derivatives inhibit SFKs/Stat signaling associated with apoptosis in human cancer cells

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
S Nam ◽  
R Buettner ◽  
X Liu ◽  
J Turkson ◽  
D Kim ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Stat Signaling

Progesterone-independent induction of decidualization of endometrial stromal cells of patients with and without endometriosis

2015 ◽  
Vol 75 (07) ◽  
Author(s):  
J Thomczik ◽  
I Beyer ◽  
DM Baston-Büst ◽  
SJ Böddeker ◽  
G Wennemuth ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Endometrial Stromal Cells

Regulation of TIMP-1, -2 and -3 in human endometrial stromal cells during decidualization and under the influence of hCG

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
S Krenzer ◽  
H Fluhr ◽  
M Deperschmidt ◽  
M Zwirner ◽  
D Wallwiener ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Endometrial Stromal Cells

ÜBER DIE BILDUNG VON ENDOMETRIALEN KÖRNCHENZELLEN BEI KASTRATINNEN UNTER HORMONEINFLUSS

1960 ◽  
Vol XXXIII (II) ◽  
pp. 261-276 ◽  
Author(s):  
G. Hellweg ◽  
J. Ferin ◽  
K. G. Ober
Keyword(s):  
Hormone Therapy ◽  
Stromal Cells ◽  
Sex Hormone ◽  
Substitution Therapy ◽  
Secretory Phase ◽  
Hormone Substitution ◽  
Endometrial Stromal Cells ◽  
Endometrial Stroma ◽  
K Cells

ABSTRACT 65 endometrial biopsies from castrated women who had received either natural or artificial sex hormone therapy were studied microscopically. Attention was paid to various histologic criteria, especially to the number of endometrial granulocytes (»K« cells, KZ). The following was obtained: The »K« cells are completely absent when no hormone substitution therapy is given. They were also lacking when the castrated patients were treated only with oestrogens, even if the dose given was ten-times that found in women during the reproductive ages. In contrast, the »K« cells developed from the endometrial stromal cells only under influence of progesterone, usually appearing first 8–10 days after the administration of the gestagen. The »K« cells were demonstrable in the number corresponding to a normal secretory phase only then, when the oestrogen-progesterone dosage ratio had induced a fully-developed secretory change, as measured by the usual histologic criteria. With an overdosage of oestrogen the »K« cells were either absent or were very sparse. Contrarily, an overdosage of progesterone had no influence on their number. The development of endometrial glands does not always entirely parallel that of the stroma in castrated patients following hormone therapy. A more exact indicator for the proper dose for the production of a secretory phase by hormone therapy seems to be the number of »K« cells in the endometrial stroma.

Inhibition of TMEM16A impedes embryo implantation and decidualization in mice

Reproduction ◽  
2018 ◽  
Author(s):  
Qianrong Qi ◽  
Yifan Yang ◽  
Kailin Wu ◽  
Qingzhen Xie
Keyword(s):  
Progesterone Receptor ◽  
Stromal Cells ◽  
Embryo Implantation ◽  
Mouse Uterus ◽  
Endometrial Stromal Cells ◽  
Uterine Endometrium ◽  
Molecule Inhibitor ◽  
Pathway Inhibition ◽  
And Function ◽  
Reproductive Processes

Recent studies revealed that TMEM16A is involved in several reproductive processes, including ovarian estrogen secretion and ovulation, sperm motility and acrosome reaction, fertilization, and myometrium contraction. However, little is known about the expression and function of TMEM16A in embryo implantation and decidualization. In this study, we focused on the expression and regulation of TMEM16A in mouse uterus during early pregnancy. We found that TMEM16A is up-regulated in uterine endometrium in response to embryo implantation and decidualization. Progesterone treatment could induce TMEM16A expression in endometrial stromal cells through progesterone receptor/c-Myc pathway, which is blocked by progesterone receptor antagonist or the inhibitor of c-Myc signaling pathway. Inhibition of TMEM16A by small molecule inhibitor (T16Ainh-A01) resulted in impaired embryo implantation and decidualization in mice. Treatment with either specific siRNA of Tmem16a or T16Ainh-A01 inhibited the decidualization and proliferation of mouse endometrial stromal cells. In conclusion, our results revealed that TMEM16A is involved in embryo implantation and decidualization in mice, compromised function of TMEM16A may lead to impaired embryo implantation and decidualization.

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