PI3K/AKT pathway activation in bladder carcinogenesis. Issue 8 (24th October 2013)

• Record Type: Journal Article
• Authors: Calderaro, Julien; Rebouissou, Sandra; de, Leanne; Masmoudi, Asma; Hérault, Aurélie; Dubois, Thierry; Maille, Pascale; Soyeux, Pascale; Sibony, Mathilde; de la, Alexandre; Vordos, Dimitri; Lebret, Thierry; Radvanyi, François; Allory, Yves
• Is Part Of: International journal of cancer. Volume 134:Issue 8(2014:Apr. 15)
• Page Start: 1776
• Page End: 1784
• Publication Date: 2013-10-24
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28518
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The PI3K/AKT pathway is considered to play a major role in bladder carcinogenesis, but its relationships with other molecular alterations observed in bladder cancer remain unknown. We investigated PI3K/AKT pathway activation in a series of human bladder urothelial carcinomas (UC) according to PTEN expression, <italic>PTEN</italic> deletions and <italic>FGFR3, PIK3CA, KRAS, HRAS, NRAS</italic> and <italic>TP53</italic> gene mutations. The series included 6 normal bladder urothelial samples and 129 UC (Ta <italic>n</italic> = 25, T1 <italic>n</italic> = 34, T2–T3–T4 <italic>n</italic> = 70). Expression of phospho‐AKT (pAKT), phospho‐S6‐Ribosomal Protein (pS6) (one downstream effector of PI3K/AKT pathway) and PTEN was evaluated by reverse phase protein Array. Expression of miR‐21, miR‐19a and miR‐222, known to regulate PTEN expression, was also evaluated. pAKT expression levels were higher in tumors than in normal urothelium (<italic>p</italic> < 0.01), regardless of stage and showed a weak and positive correlation with pS6 (Spearman coefficient <italic>R</italic><sub>S</sub> = 0.26; <italic>p</italic> = 0.002). No association was observed between pAKT or pS6 expression and the gene mutations studied. PTEN expression was decreased in <italic>PTEN</italic>‐deleted tumors, and in T1 (<italic>p</italic> = 0.0089) and T2–T3–T4 (<italic>p</italic> < 0.001) tumors compared to Ta tumors; it was also negatively correlated with miR‐19a (<italic>R</italic><sub>S</sub> = −0.50; <italic>p</italic> = 0.0088) and miR‐222 (<italic>R</italic><sub>S</sub> = −0.48; <italic>p</italic> = 0.0132), but not miR‐21 (<italic>R</italic><sub>S</sub> = −0.27; <italic>p</italic> = 0.18) expression. pAKT and PTEN expressions were not negatively correlated, and, on the opposite, a positive and moderate correlation was observed in Ta (<italic>R</italic><sub>S</sub> = 0.54; <italic>p</italic> = 0.0056) and T1 (<italic>R</italic><sub>S</sub> = 0.56; <italic>p</italic> = 0.0006) tumors. Our study suggests that PI3K/AKT pathway activation occurs in the entire spectrum of bladder UC regardless of stage or known most frequent molecular alterations, and independently of low PTEN expression.</p> </abstract>