A Progesterone Responsive Gene, 14-3-3 Tau, Upregulates the Transcriptional Activity of Progesterone Receptor B (PR-B) in Uterine Endometrium.

2010 ◽  
pp. P3-14-P3-14
Author(s):  
M Ito ◽  
H Hiroi ◽  
T Urano ◽  
M Momoeda ◽  
Y Hosokawa ◽  
...  
Author(s):  
Haizhen Wang ◽  
Zhenghua Tang ◽  
Ting Li ◽  
Menglu Liu ◽  
Yong Li ◽  
...  

Medroxyprogesterone (MPA) is used for the conservative treatment of endometrial cancer. Unfortunately, progesterone resistance seriously affects its therapeutic effect. The purpose of the current study was to investigate the influence of deletion of AT-rich interactive domain 1A (ARID1A) in progesterone resistance in Ishikawa cells. Ablation of ARID1A was conducted through the CRISPR/Cas9 technology. Acquired progesterone-resistant Ishikawa (Ishikawa-PR) cells were generated by chronic exposure of Ishikawa cells to MPA. The sensitivity of the parental Ishikawa, Ishikawa-PR, and ARID1A-deficient cells to MPA and/or LY294002 was determined using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. In addition, Western blot analysis and reverse transcription-polymerase chain reaction was performed to evaluate the mRNA and protein expression levels of ARID1A, progesterone receptor B (PRB), and P-AKT. Both Ishikawa-PR and ARID1A knockout cells showed insensitivity to MPA, downregulation of PRB, and hyperphosphorylation of AKT compared to the parental Ishikawa cells. Pretreatment with LY294002 significantly enhanced the ability of MPA to suppress proliferation and to induce apoptosis in the parental and Ishikawa-PR cells via the inhibition of AKT activation and upregulation of PRB transcriptional activity. However, the PRB transcriptional activity and insensitivity to MPA were irreversible by LY294002 in ARID1A-deficient cells. Ablation of ARID1A is associated with low PRB expression, which serves an important role in primary progesterone resistance. Akt inhibition cannot rescue PRB or sensitize to MPA in ARID1A knockout cells. These findings suggest that ARID1A may act as a reliable biomarker to predict the response for the combination of AKT inhibitor and MPA treatment.


Reproduction ◽  
2018 ◽  
Author(s):  
Qianrong Qi ◽  
Yifan Yang ◽  
Kailin Wu ◽  
Qingzhen Xie

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.


Oncogene ◽  
2016 ◽  
Vol 35 (39) ◽  
pp. 5191-5201 ◽  
Author(s):  
I I Lee ◽  
K Maniar ◽  
J P Lydon ◽  
J J Kim

2020 ◽  
Vol 533 (4) ◽  
pp. 1027-1033
Author(s):  
Kim Enfield ◽  
Sigcinile Dlamini ◽  
Chanel Avenant ◽  
Michael Kuipa ◽  
Janet P. Hapgood

1984 ◽  
Vol 81 (20) ◽  
pp. 6358-6362 ◽  
Author(s):  
T. Zarucki-Schulz ◽  
M. S. Kulomaa ◽  
D. R. Headon ◽  
N. L. Weigel ◽  
M. Baez ◽  
...  

2021 ◽  
Vol 116 (3) ◽  
pp. e39-e40
Author(s):  
Tamara Garrido-Gómez ◽  
Nerea Castillo-Marco ◽  
Irene Muñoz-Blat ◽  
Teresa Cordero ◽  
Mónica Clemente-Ciscar ◽  
...  

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