ERK4, a new tumor suppressor gene candidate implicated in prostate cancer progression
Notice bibliographique
Résumé
In Canada, prostate cancer is the most frequently diagnosed cancer in man and the third leading cause of cancer related death. In order to identify genes implicated in prostate cancer progression, we used microcell-mediated chromosome transfer to introduce chromosomes 10, 12, 17 and 18 into human PC-3-derived cells lines called PC-3M-Pro4GP1 and PC-3M-LN4GP2. The properties of the hybrids were determined by invasion assay, growth in soft agar and injection into nude mice (either subcutaneously or orthotopically). After the transfer of chromosome 18 in our cell lines, we have identified two sets of hybrids that show opposite phenotypes. Genotyping studies indicated that one locus on chromosome 18 (D18S51) contains an additional allele in the less tumorigenic hybrids. This allele is absent in the highly tumorigenic hybrids as well as in tumors derived from the injection of less tumorigenic cells into nude mice. Preliminary microarray data analysis showed that two genes located in the D18S51 region (ERK4 and BCL2) were differentially expressed in the less tumorigenic hybrids compared to the tumorigenic hybrids. We examined publicly available microarray data sets and found that ERK4 was down regulated in prostate, adrenal and lung cancers. We have also examined the possibility that the metastasis suppressor gene MASPIN (also located in the D18S51 region) could be responsible for the less tumorigenic phenotype seen in our hybrids. Real-time PCR studies showed that ERK4 and MASPIN were up regulated in the less tumorigenic hybrids and that BCL2 was down regulated in these same cells. However, Western immunoblot experiments did not show any difference in the MASPIN or the BCL2 protein levels. Thus, MASPIN or a BCL2 repressor are most likely not responsible for the less tumorigenic phenotype of our hybrids. Interestingly, re-introduction of ERK4 in our tumorigenic hybrids completely abolished their ability to form colonies in soft agar and to invade through Matrigel. However, there is no difference in tumor growth rate upon injection of ERK4-over-expressing cells compared to mock-transfected controls. We also found a non-synonymous polymorphism in the coding sequence of the ERK4 gene. This polymorphism is present at the same frequency in Asian, European and Ashkenazi Jewish populations but less frequently in the African (Yoruba) population. This is the first report of a non-synonymous polymorphism in the coding sequence of the ERK4 gene. However, based on a limited number of prostate cancer cases, the presence of this poylmorphism is not associated with the disease. Taken together, these results demonstrate that ERK4 is a good candidate for a tumor suppressor gene implicated in prostate cancer progression.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| 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) | 0,002 | 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 source (Gemma direct ou Codex distillé), 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 ».