expression of GPR54 and KiSS1 in human breast cancer
Notice bibliographique
Résumé
4317 Metastatic breast cancer is the second most common cause of death due to cancer in women. Metastin is a 54 amino acid kisspeptide that was characterized as anti-metastatic using in vitro and in vivo studies in a human melanoma cell line. The kisspeptins (Kp10, Kp13, Kp14, and Kp54) are encoded by the KiSS1 gene which is located on chromosome 1q32. The kisspeptin receptor is GPR54 , a G coupled receptor, whose gene is located at chromosome 19p13. Mutated GPR54 is found in humans with hypogonadotropic hypogonadism and GPR54 null mice do not undergo puberty. The kisspeptins stimulate release of LH and FSH through the release of GnRH via the hypothalamo-pituitary axis in mice and humans. As well as having an endocrine function, these genes have also been demonstrated to have an autocrine/paracrine function. Both are expressed in syncytiotrophoblast cells and are thought to control trophoblast invasion during pregnancy. Therefore, metastasis development in breast cancer may in part be determined by GPR54 and KiSS1 expression. Using tissue microarray (TMA) technology, 438 cases of clinical breast cancers with linked outcome data have been assessed for gene copy number of KiSS1 and GPR54 using florescent in situ hybridization (FISH). Using the KiSS1 fluorescent probe, it was discovered that 29/233 breast cancer cases were amplified (12.4%), while only 3 cases showed loss of gene copy number. There was no correlation with survival or ER status. For the GPR54 fluorescent probe, 27/191 cases showed gene loss (14%) while 4 cases were amplified. GPR54 loss correlates with poor survival in node positive patients (p=0.0071). To further assess gene expression, the breast cancer cell lines MDA-MB-231 and MCF-7 were assessed for GPR54 and KiSS1 mRNA levels using real time PCR. Non-metastatic MCF-7 breast cancer cells showed high levels of both GPR54 and KiSS1 expression as compared to the immortalized H-tert breast cell line. Metastatic MDA-MB-231 breast cancer cell line demonstrated increased KiSS1 expression as compared to H-terts but relatively little GPR54 expression as compared to MCF-7 cells or H-tert cells. Western blot analysis confirmed these findings, demonstrating visible GPR54 expression in the MCF-7 protein lysates only. FISH was used on metaphases of MDA-MB-231, MCF-7 and H-tert cells to determine if gene copy number reflected the expression levels. The MDA-MB-231 cells showed three copies of KiSS1 and two to three copies of GPR54 . The MCF-7 cells showed five copies of KiSS1 and two copies of GPR54 , whereas the H-tert cells demonstrated the expected normal two copies of each gene. Loss of GPR54 gene copy number in clinical breast cancer cases of node positive patients and the loss of GPR54 expression in the MDA-MB-231 cell line supports the hypothesis that breast cancer metastasis is in part regulated by GPR54 expression. For the MDA-MB-231 cell line, loss of GPR54 expression may be determined by epigenetic factors.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».