Abstract 3018: Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the invasiveness of endometrial cancer cells through GnRH-I receptor and mitogen-activated protein kinases (MAPKs)-dependent activation of matrix metalloproteinase (MMP)-2
Bibliographic record
Abstract
Abstract Introduction: More than 25% of patients diagnosed with endometrial carcinoma have an invasive primary cancer accompanied by metastases. The GnRH has an important role in reproduction. In mammals, GnRH-II is more widely identified than GnRH-I in peripheral tissues. GnRH-II may regulate tumor progression of endometrial cancer. MAPKs have been considered important components of GnRH-induced signaling pathways. MMPs are largely implicated in promoting angiogenesis and tumor metastasis. In the present study, we examined the action of GnRH-II agonist-promoted motility of endometrial cancer cells and the mechanisms of the action in endometrial cancer. Materials and methods: Endometrial cancer cell line Ishikawa and ECC-1 were derived from an endometrial adenocarcinoma. D-Arg6, AzaGly10-GnRH II was a synthetic decapeptide. Cell motility was estimated by invasion and migration assay. The activities of MMP-2 was assessed by gelatin zymography. Immunoblot analysis was done to study the expression of GnRH-I receptor and the effects of GnRH-II agonist in the activation of ERK1/2, JNK and MMP-2. ERK1/2 inhibitor (U0126), and JNK inhibitor (SP600125) were pretreated for 30 min to evaluate the effects of MAPKs. MMP-2 inhibitor (OA-Hy) was pretreated for 30 min to evaluate the effects of MMP-2 in cell motility. Human GnRH-I receptor siRNA was used to knock down the expression of GnRH-I receptor. Results: The GnRH-I receptor was expressed in endometrial cancer cells. The GnRH-II agonist promoted cell motility in a dose-dependent manner. GnRH-II agonist activated the phosphorylation of ERK1/2 and JNK signaling and the phosphorylation was abolished by 1μM U0126 and 1μM SP600125. GnRH-II agonist-promoted cell motility was suppressed in cells pretreated with U0126 and SP600125. Moreover, U0126 and SP600125 abolished GnRH-II agonist-induced activation of MMP-2. Inhibition of MMP-2 with 10μM OA-Hy suppressed cell motility in response to GnRH-II agonist. GnRH-II agonist-mediated cell motility was suppressed by knockdown of endogenous GnRH-I receptor with siRNA. Conclusion: Our results confirmed that GnRH-I receptor may be a common receptor that mediates the effects of both GnRH-I and GnRH-II in endometrial cancer cells. Our study shows that the GnRH-II agonist promoted the cell motility of endometrial cancer cells through the GnRH-I receptor, and the phosphorylation of ERK1/2 and JNK-dependent activation of MMP-2. Our findings represent a new concept regarding the mechanisms of GnRH-II-promoted cell motility in endometrial cancer cells, suggesting the possibility of GnRH-II as a potential therapeutic intervention for the treatment of human endometrial cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3018. doi:1538-7445.AM2012-3018
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".