title: Stage-dependent expression of PI3K/Akt‑pathway genes in neuroblastoma.
abstract: The phosphoinositide-3 kinase (PI3K) pathway plays a critical role in cancer             cell growth and survival and has also been implicated in the development of the             childhood cancer neuroblastoma. In neuroblastoma high mRNA expression of the PI3K             catalytic isoform PIK3CD is associated to favorable disease. Yet, activation of             Akt is associated with poor prognosis. Since the contribution of the numerous             members of this pathway to neuroblastoma pathogenesis is mainly unknown, genes             of the PI3K/Akt pathway were analyzed at the mRNA level through microarrays and             quantitative real-time RT-PCR (TaqMan) and at the protein level using western             blot analysis. Five genes showed lower mRNA expression in aggressive compared             to more favorable neuroblastomas (PRKCZ, PRKCB1, EIF4EBP1, PIK3RI and PIK3CD)             while the opposite was seen for PDGFRA. Clustering analysis shows that the expression             levels of these six genes can predict aggressive disease. At the protein level,             p110δ (encoded by PIK3CD) and p85α isomers (encoded by PIK3R1) were more highly             expressed in favorable compared to aggressive neuroblastoma. Evaluation of the             expression of these PI3K genes can predict aggressive disease, and indicates stage-dependent             involvement of PI3K-pathway members in neuroblastoma.
authors.affiliation: Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, Gothenburg University, Gothenburg, Sweden. susanne.fransson@clingen.gu.se
authors.forename: Susanne
authors.initials: S
authors.lastname: Fransson
authors.forename: Frida
authors.initials: F
authors.lastname: Abel
authors.forename: Per
authors.initials: P
authors.lastname: Kogner
authors.forename: Tommy
authors.initials: T
authors.lastname: Martinsson
authors.forename: Katarina
authors.initials: K
authors.lastname: Ejeskär
mesh_terms: D058534:Class I Phosphatidylinositol 3-Kinases; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C486018:PIK3CD protein, human; D051058:Oncogene Protein v-akt