Gefitinib enhances sensitivity of endometrial cancer cells to progestin therapy via dual-specificity phosphatase 1

Yang, Yuan; Zhou, Jingyi; Li, Xiaoping; Zhao, Lijun; Cheng, Yuan; Lin, Yanying; Wang, Jianliu; Wei, Lihui; Dong, Yafeng

doi:10.18632/oncotarget.23264

Cited by 6 publications

(5 citation statements)

References 39 publications

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“…For this reason, obtaining an optimal progesterone transcription level is important and could set the stage for effective precision dual therapy with progestin and a tyrosine kinase inhibitor in endometrial cancer patients. This is an approach that, albeit not yet personalized, has started to attract attention and bear fruits 40 , 41 , while Systems biology methods could help find conditions to activate and protect enough PR from ubiquitination, promoting maximal transcription and allowing for progestin treatment.…”

Section: Resultsmentioning

confidence: 99%

Stochastic model of ERK-mediated progesterone receptor translocation, clustering and transcriptional activity

Marquez‐Lago

Steinberg

2022

Sci Rep

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Progesterone receptor (PR) transcriptional activity is a key factor in the differentiation of the uterine endometrium. By consequence, progestin has been identified as an important treatment modality for endometrial cancer. PR transcriptional activity is controlled by extracellular-signal-regulated kinase (ERK) mediated phosphorylation, downstream of growth factor receptors such as EGFR. However, phosphorylation of PR also targets it for ubiquitination and destruction in the proteasome. Quantitative studies of these opposing roles are much needed toward validation of potential new progestin-based therapeutics. In this work, we propose a spatial stochastic model to study the effects of the opposing roles for PR phosphorylation on the levels of active transcription factor. Our numerical simulations confirm earlier in vitro experiments in endometrial cancer cell lines, identifying clustering as a mechanism that amplifies the ability of progesterone receptors to influence gene transcription. We additionally show the usefulness of a statistical method we developed to quantify and control variations in stochastic simulations in general biochemical systems, assisting modelers in defining minimal but meaningful numbers of simulations while guaranteeing outputs remain within a pre-defined confidence level.

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Section: Resultsmentioning

confidence: 99%

Stochastic model of ERK-mediated progesterone receptor translocation, clustering and transcriptional activity

Marquez‐Lago

Steinberg

2022

Sci Rep

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“…Progesterone treatment in the early stages of EC has a better therapeutic effect in improving the survival rate and reducing the risk of treatment. Patients with intermediate and advanced stages undergo surgery or chemotherapy combined with drugs such as gefitinib (27) and cisplatin (28); however, the prognosis is still poor (29). Therefore, the study of its pathological mechanism is urgent.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA JPX promotes endometrial carcinoma progression via janus kinase 2/signal transducer and activator of transcription 3

Xiong,

Zhang,

Xie

et al. 2024

Front. Oncol.

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IntroductionAlthough LncRNA JPX has been linked to a number of malignancies, it is yet unknown how it relates to endometrial carcinoma (EC). Investigating the expression, functional activities, and underlying molecular processes of lncRNA JPX in EC was the goal of this work.MethodsRT-qPCR was used to examine the differences in lncRNA/microRNA (miRNA, miR)/mRNA expression between normal cervical and EC tissues or cells. Cell Counting Kit-8, flow cytometry, and transwell were used to evaluate the association between lncRNA JPX/miR-140-3p/phosphoinositide-3-kinase catalytic subunit α (PIK3CA) in Ishikawa and JEC cell lines. The impact of JPX on the downstream janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling pathway was investigated using Western blot analysis.ResultsWhen comparing EC tissues to nearby normal tissues, JPX expression is markedly increased in EC tissues, with greater expression in advanced-stage EC. Furthermore, compared to normal epithelial cells, EC cell lines have higher levels of JPX expression. In Ishikawa and JEC endometrial cancer cell lines, we used siRNA-mediated suppression of JPX to find lower cell viability, increased apoptosis, cell cycle arrest, and reduced migration and invasion. We next verified that miR-140-3p binds to downstream target cells to impede the transcription and translation of PIK3CA, which in turn prevents the growth of Ishikawa and JEC cells. JPX functions as a ceRNA to adsorb miR-140-3p. This procedure required controlling JAK2/STAT3, a downstream signal.ConclusionJPX enhances the development of Ishikawa and JEC cells and activates downstream JAK2/STAT3 signal transduction via the miR-140-3p/PIK3CA axis, offering a possible therapeutic target for the treatment of EC.

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“…Total protein was extracted and quantified according to the manufacturer's instructions. Western blot assay was performed as described previously [18] anti -Cav1.3 polyclonal antibody (1:1000, Abcam, USA), cleaved caspase 3/caspase 3 (1:1000, Abcam, USA), cleaved PARP/PARP (1:1000, Abcam, USA) were used. Use ECL substrate to detect its expression.…”

Section: Western Blot Assaymentioning

confidence: 99%

Ca2+ channel subunit a 1D inhibits endometriosis cell apoptosis and mediated by prostaglandin E2

Yang¹,

Yuan²,

Ma³

et al. 2019

Ginekol Pol

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Objectives: Endometriosis is considered as a chronic pelvic inflammatory disease and prostaglandin E2(PGE2) (a kind of the inflammatory cytokines) was increased in the endometriosis patient's peritoneal fluid . Ca2+ signal and Ca2+ channels play an important role in cell apoptosis. This study was to explore the L-type calcium channel (Cav1.3) expression and its biological function in endometriosis. Furthermore the molecular mechanism between Cav1.3 and PGE2 was also clarified. Material and methods:The real-time PCR and immunohistochemical were used to detect the expression of Cav1.3. Apoptosis was detected by Flow cytometry assay and Western blot assay.Results: Cav1.3 was high expression in endometriosis tissue and primary endometrial stromal cells (hEM15A). Treatment with PGE2 rapidly inhibited apoptosis and increased Cav1.3 expression in hEM15A . The silencing of Cav1.3 promoted apoptosis, which was unchanged after PGE2 treatment. Moreover, the inhibition of Cav1.3 by shRNA transfection activated cleaved PARP and cleaved caspase-3. Conclusions:These available evidences suggest that Cav1.3 is required for PGE2 induction apoptosis and relates to the pathophysiology of endometriosis. Interference with Cav1.3 may offer a neo-therapeutic window in endometriosis treatment.

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Gefitinib enhances sensitivity of endometrial cancer cells to progestin therapy via dual-specificity phosphatase 1

Cited by 6 publications

References 39 publications

Stochastic model of ERK-mediated progesterone receptor translocation, clustering and transcriptional activity

Stochastic model of ERK-mediated progesterone receptor translocation, clustering and transcriptional activity

Long non-coding RNA JPX promotes endometrial carcinoma progression via janus kinase 2/signal transducer and activator of transcription 3

Ca2+ channel subunit a 1D inhibits endometriosis cell apoptosis and mediated by prostaglandin E2

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