| General information | Literature | Expression | Regulation | Mutation | Homolog | Interaction |
Basic Information | |
|---|---|
Gene ID | 2797 |
Name | GNRH2 |
Synonymous | gonadotropin-releasing hormone 2;GNRH2;gonadotropin-releasing hormone 2 |
Definition | luliberin II|luteinizing hormone-releasing hormone II|progonadoliberin II|progonadoliberin-2 |
Position | 20p13 |
Gene type | protein-coding |
Title | Abstract |
| ovarian cancer | GnRH-II is produced by ovarian cancer cells and enhances their invasiveness in vitro. In our studies of OVCAR-3 and CaOV-3 ovarian cancer cell lines, GnRH-II treatment induced phosphorylation of Akt and glycogen synthase kinase (GSK)3beta, as well as beta-catenin accumulation in the nucleus, and the latter was reduced by small interfering RNA (siRNA)-mediated depletion of the GnRH receptor. The phosphatidylinositol 3 kinase (PI3K)/Akt pathway is involved in beta-catenin-dependent signaling, and pretreatment of these human ovarian cancer cells with a PI3K/Akt inhibitor, LY294002, attenuated GnRH-II-stimulated phosphorylation of GSK3beta and inhibited GnRH-II-induced invasion. It also attenuated GnRH-II induced trans-activation of a beta-catenin-dependent reporter gene, most likely because GSK3beta phosphorylation promotes translocation of beta-catenin to the nucleus. Membrane type I matrix metalloproteinase (MT1-MMP) contributes to tumor progression directly, or by processing the latent MMP-2 zymogen, and is a known target of beta-catenin signaling. When OVCAR-3 and CaOV-3 cells were treated with GnRH-II, MT1-MMP levels increased approximately 3-fold, whereas siRNA-mediated depletion of GnRH receptor or pretreatment with LY294002 abrogated this. In addition, lithium chloride, which increases GSK3beta phosphorylation and the nuclear translocation of beta-catenin, increased MT1-MMP levels in these ovarian cancer cells. By contrast, depletion of beta-catenin by siRNA treatment abolished GnRH-II-induced MT1-MMP synthesis and reduced their invasive potential. Furthermore, siRNA-mediated reduction of MT1-MMP levels reduced GnRH-II-induced invasion in ovarian cancer cells. We therefore conclude that GnRH-II stimulates the PI3K/Akt pathway, and the phosphorylation of GSK3beta, thereby enhancing the beta-catenin-dependent up-regulation of MT1-MMP production, which contributes to ovarian cancer metastasis. |