Fas and Fas ligand system may mediate antiproliferative activity of gonadotropin-releasing hormone receptor in endometrial cancer cells.

Imai, Atsushi; Takagi, Atsushi; Horibe, Shinji; Tamaya, Teruhiko

doi:10.3892/ijo.13.1.97

Cited by 21 publications

(13 citation statements)

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“…In addition, it was described that GnRH controls FAS and FASL expression in other cell types [47,48]. Therefore, we decided to evaluate the protein expression of these cytokines.…”

Section: Protein Levels Of Fas and Fasl In Antral Folliclesmentioning

confidence: 99%

Gonadotropin-Releasing Hormone Antagonist Antide Inhibits Apoptosis of Preovulatory Follicle Cells in Rat Ovary1

Parborell

Irusta

Vitale

et al. 2005

Biology of Reproduction

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Analogs of GnRH, including agonists (GnRH-a) and antagonists (GnRH-ant), have been widely used to inhibit gonadotropin pituitary release. Aside from the effect of GnRH analogs on the pituitary-gonadal axis, studies have shown that GnRH has extrapituitary effects, particularly on rat and human ovaries. In the present study, we evaluated the direct in vivo effects of the GnRH-a, leuprolide acetate (LA), or the GnRH-ant, Antide (Ant), either singly or together, on ovarian follicular development in prepubertal eCG-treated rats. LA significantly decreased ovarian weight, whereas Ant increased ovarian weight compared with controls; however, coinjection of both compounds had no effect. In addition, LA increased the number of preantral follicles (PFs) and atretic follicles, and decreased the number of early antral follicles (EAFs) and preovulatory follicles (POFs). Coinjection of Ant interfered with this LA effect. Ant alone increased the number of POFs compared with that of controls. Analysis of apoptosis has shown that LA increases the percentage of apoptotic cells in PFs, EAFs, and POFs; however, Ant prevented this effect. In addition, Ant alone decreased the percentage of apoptotic cells in EAFs and POFs. Data have shown that Ant per se inhibited BAX translocation from cytosol to mitochondria and retained cytochrome C in the mitochondria, whereas LA induced cytochrome C release. We conclude that Ant inhibits apoptosis in preovulatory follicles through a decrease of BAX translocation to mitochondria, suggesting that GnRH may act as a physiological intraovarian modulator factor that is able to interfere with follicular development through an increase in apoptotic events mediated by an imbalance among the BCL-2 family members.

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“…In addition, it was described that GnRH controls FAS and FASL expression in other cell types [47,48]. Therefore, we decided to evaluate the protein expression of these cytokines.…”

Section: Protein Levels Of Fas and Fasl In Antral Folliclesmentioning

confidence: 99%

Gonadotropin-Releasing Hormone Antagonist Antide Inhibits Apoptosis of Preovulatory Follicle Cells in Rat Ovary1

Parborell

Irusta

Vitale

et al. 2005

Biology of Reproduction

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“…The growth inhibitory effects of GnRH-I-a have also been observed in normal OSE cells [20]. Moreover, several reports suggest that GnRH-I-a may modulate cell growth through the induction of apoptosis in ovarian cancers [21][22][23][24][25]. Like GnRH-I, GnRH-II may have an anti-proliferative effect in immortalized OSE cells and ovarian cancer cells [13, [26][27][28][29].…”

Section: Introductionmentioning

confidence: 98%

Differential role of gonadotropin-releasing hormone on human ovarian epithelial cancer cell invasion

Chen

Cheung

Lau

et al. 2007

Endocr

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Ovarian cancer is the most lethal of all gynecological cancers. Most deaths from ovarian cancer are due to widespread intraperitoneal metastases and malignant ascites. However, mechanisms of invasion in ovarian cancer remain poorly understood. In this study, we examined the effects of gonadotropin-releasing hormone (GnRH)-I (the classical mammalian GnRH), GnRH-II (a second form of GnRH), and GnRH receptor on invasion using two human ovarian carcinoma cell lines, OVCAR-3 and SKOV-3. Here we demonstrated that in OVCAR-3, GnRH-I and GnRH-II promoted cell invasion, whereas in SKOV-3, GnRH-I and GnRH-II inhibited cell invasion. Transfection of small interfering RNA to abrogate the gene expression of GnRH receptor reversed GnRH-I and GnRH-II-mediated invasion activities, suggesting that the same receptor, type I GnRH receptor, is essential for the effects of GnRH-I and GnRH-II in both OVCAR-3 and SKOV-3. Treatment of SKOV-3 cells with GnRH-I or GnRH-II resulted in a decrease in matrix metalloproteinase 2 but an increase in tissue inhibitor of metalloproteinase 2 secretions. In addition, we found that GnRH-I and GnRH-II interfered with activation of the phosphatidylinositol-3-kinase/AKT pathway that is well documented to stimulate proteolysis and invasion of ovarian cancer cells. Taken together, these observations suggest that GnRH-I and GnRH-II play key regulatory roles in ovarian tumor cell invasion and extracellular matrix degradation.

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“…In endometrial cancer cell lines expressing growth hormone releasing hormone (GHRH) receptors, GHRH antagonists induce apoptosis and this action is thought to be partly mediated by CD95/CD95L pathway [50]. Similarly, gonadotropin releasing hormone (GnRH) analogs induce apoptosis in GnRHexpressing endometrial cancer cells [51]. Mifeprestone also induces apoptosis in Ishikawa endometrial cancer cell lines, mediated partly by the CD95/CD95L pathway [52].…”

Section: Cd95/cd95lmentioning

confidence: 97%

Therapeutic targeting of the TNF superfamily: A promising treatment for advanced endometrial adenocarcinoma

Thangaraju¹,

Subramani²,

Chakravarty³

et al. 2012

Gynecologic Oncology

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Fas and Fas ligand system may mediate antiproliferative activity of gonadotropin-releasing hormone receptor in endometrial cancer cells.

Cited by 21 publications

References 0 publications

Gonadotropin-Releasing Hormone Antagonist Antide Inhibits Apoptosis of Preovulatory Follicle Cells in Rat Ovary1

Gonadotropin-Releasing Hormone Antagonist Antide Inhibits Apoptosis of Preovulatory Follicle Cells in Rat Ovary1

Differential role of gonadotropin-releasing hormone on human ovarian epithelial cancer cell invasion

Therapeutic targeting of the TNF superfamily: A promising treatment for advanced endometrial adenocarcinoma

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