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High level of p37δ-mRNA relative to p110δ-mRNA in neuroblastoma tumors correlates with poor patient survival
Sahlgrenska Cancer Center, University of Gothenburg, Sweden.
Högskolan i Skövde, Institutionen för vård och natur. Högskolan i Skövde, Forskningscentrum för Systembiologi. Sahlgrenska Cancer Center, University of Gothenburg, Sweden.ORCID-id: 0000-0001-8962-0860
2013 (engelsk)Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 30, nr 4, artikkel-id 724Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Alterations in the PI3K/Akt pathway, a pathway that promotes proliferation and oncogenic transformation, are common in various cancers. In neuroblastoma, activation of Akt is correlated with aggressive disease although mutations in genes of this pathway are rare. Previous findings include a few mutations in PIK3CD, the gene encoding PI3K catalytic subunit delta, p110delta. We recently reported that an alternatively spliced form of p110delta, called p37delta, had cell proliferative properties and was over-expressed in ovarian and colorectal tumors. Here, we investigated p37delta in neuroblastoma primary tumors of different stages using qPCR (TaqMan) for gene expression analysis (46 samples) and Western blot for protein analysis (22 samples). Elevated levels of both p37delta-mRNA and p110delta-mRNA were detected in metastasizing neuroblastoma tumors compared to normal adrenal gland (P<0.05), and higher expression of p37delta-mRNA relative to p110delta-mRNA in neuroblastoma non-survivor patients compared to survivors (P<0.01). p37delta-Protein levels but not p110delta levels correlated with increased pAKT(T308) and pERK levels. The p37delta-mRNA levels did not correlate with the protein levels, indicating major regulation at the translational/protein level. Deregulation of signaling pathways is a hallmark of cancer development. Here, we show that p37delta, a kinase-dead isoform of the PI3K catalytic subunit p110delta, is over-expressed in neuroblastoma tumors, and that it correlates with the activation of both PI3K/Akt- and RAS-signaling pathways.

sted, utgiver, år, opplag, sider
Springer Science+Business Media B.V., 2013. Vol. 30, nr 4, artikkel-id 724
Emneord [en]
p110d, p37d, Neuroblastoma, PI3K
HSV kategori
Forskningsprogram
Naturvetenskap
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URN: urn:nbn:se:his:diva-8596DOI: 10.1007/s12032-013-0724-3ISI: 000327858800039PubMedID: 24026661Scopus ID: 2-s2.0-84883626316OAI: oai:DiVA.org:his-8596DiVA, id: diva2:660653
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Alternativ titel: High level of p37delta-mRNA relative to p110delta-mRNA in neuroblastoma tumors correlates with poor patient survival

Tilgjengelig fra: 2013-10-30 Laget: 2013-10-30 Sist oppdatert: 2017-12-06bibliografisk kontrollert

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