Mifepristone attenuates human chorionic gonadotropin–induced extracellular signal–regulated kinase 1/2 phosphorylation, cyclooxygenase-2, and prostaglandin E2 production in human granulosa luteal cells

Tsai, Eing‐Mei; Chan, Te-Fu; Chen, Yung-Hung; Hsu, Sodio C. N.; Chuang, Chiao-Ya; Lee, Jau-Nan

doi:10.1016/j.fertnstert.2007.05.053

Cited by 17 publications

(4 citation statements)

References 48 publications

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“…Using the ERK1/2 phosphorylation blocker PD98059, we discovered that MMP-2 upregulation resulted from ERK1/2 phosphorylation. ERK1/2 have been proved to contribute to tumor proliferation, migration and metastasis, and several studies reported that hCG promoted the ERK1/2 activation in some cell types [30], [31]. Obviously, these results are consistent with our results that hCG induced ERK1/2 phosphorylation in a dose- and time-dependent manners in DU145 cells.…”

Section: Discussionsupporting

confidence: 93%

Human Chorionic Gonadotropin β Induces Migration and Invasion via Activating ERK1/2 and MMP-2 in Human Prostate Cancer DU145 Cells

et al. 2013

PLoS ONE

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We previously demonstrated that human chorionic gonadotropin β (hCGβ) induced migration and invasion in human prostate cancer cells. However, the involved molecular mechanisms are unclear. Here, we established a stable prostate cancer cell line overexpressing hCGβ and tested hCGβ-triggered signaling pathways causing cell migration and invasion. ELISA showed that the hCGβ amount secreted into medium increased with culture time after the hCGβ-transfected cells were incubated for 3, 6, 9, 12 and 24 h. More, hCGβ standards promoted MAPK (ERK1/2) phosphorylation and increased MMP-2 expression and activity in both dose- and time-dependent manners in hCGβ non-transfected cells. In addition, hCGβ promoted ERK1/2 phosphorylation and increased MMP-2 expression and activity significantly in hCGβ transfected DU145 cells. Whereas ERK1/2 blocker PD98059 (25 µM) significantly downregulated phosphorylated ERK1/2 and MMP-2. Particularly, hCGβ promoted cell migration and invasion, yet the PD98059 diminished the hCGβ-induced cell motility under those conditions. These results indicated that hCGβ induced cell motility via promoting ERK1/2 phosphorylation and MMP-2 upregulation in human prostate cancer DU145 cells.

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Section: Discussionsupporting

confidence: 93%

Human Chorionic Gonadotropin β Induces Migration and Invasion via Activating ERK1/2 and MMP-2 in Human Prostate Cancer DU145 Cells

et al. 2013

PLoS ONE

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“…The dosage of inhibitors was chosen based on previously published studies (19, 24, 25), and our pilot study showing a dose-dependent response (data not shown). RU486 had no effect on P4 levels both in control and hCG-stimulated cells [Fig.…”

Section: Resultsmentioning

confidence: 99%

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles

Choi

Wilson

Hannon

et al. 2017

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)–like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans.Objective:To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries.Design and Participants:Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients.Main Outcome Measures:The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured.Results:PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes.Conclusions:This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells.

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“…BDMC significantly inhibited ERK1/2 but increased p-ERK1/2 in Hela cells ( Figure 5A). ERK1/2 have been shown to contribute to cancer cell proliferation, migration and metastasis in some cell lines (45,46) and increased p-ERK1/2 activity promotes cancer cell proliferation and metastasis in various cancer cell lines (47)(48)(49). Our findings indicate that BDMC reduced MMP-2 and -9 activities and protein expression, which may be via ERK1/2 phosphorylation, and it also inhibited the vimentin pathway in HeLa cells.…”

Section: Discussionmentioning

confidence: 51%

Bisdemethoxycurcumin Suppresses Migration and Invasion of Human Cervical Cancer HeLa Cells via Inhibition of NF-ĸB, MMP-2 and -9 Pathways

et al. 2018

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Mifepristone attenuates human chorionic gonadotropin–induced extracellular signal–regulated kinase 1/2 phosphorylation, cyclooxygenase-2, and prostaglandin E2 production in human granulosa luteal cells

Cited by 17 publications

References 48 publications

Human Chorionic Gonadotropin β Induces Migration and Invasion via Activating ERK1/2 and MMP-2 in Human Prostate Cancer DU145 Cells

Human Chorionic Gonadotropin β Induces Migration and Invasion via Activating ERK1/2 and MMP-2 in Human Prostate Cancer DU145 Cells

Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles

Bisdemethoxycurcumin Suppresses Migration and Invasion of Human Cervical Cancer HeLa Cells via Inhibition of NF-ĸB, MMP-2 and -9 Pathways

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