Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2Reportar como inadecuado




Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Breast Cancer Research

, 7:R394

First Online: 24 March 2005Received: 14 October 2004Revised: 09 February 2005Accepted: 28 February 2005

Abstract

IntroductionAkt1, Akt2 and Akt3 kinases are downstream components of phosphoinositol 3-kinase derived signals from receptor tyrosine kinases, which influence cell growth, proliferation and survival. Akt2 overexpression and amplification have been described in breast, ovarian and pancreatic cancers. The present study was designed to investigate the prognostic significance of activated Akt in primary breast cancer and its association with other tumour biomarkers.

MethodsUsing a two-site chemiluminescence-linked immunosorbent assay, we measured the quantitative expression levels of total phosphorylated P-S473 Akt Akt1-Akt2-Akt3 on cytosol fractions obtained from fresh frozen tissue samples of 156 primary breast cancer patients.

ResultsAkt phosphorylation was not associated with nodal status or ErbB-2 protein expression levels. High levels of phosphorylated Akt correlated P < 0.01 with poor prognosis, and the significance of this correlation increased P < 0.001 in the subset of patients with ErbB-2 overexpressing tumours. In addition, phosphorylated Akt was found to be associated with mRNA expression levels of several proliferation markers e.g. thymidylate synthase, measured using quantitative real-time RT-PCR.

ConclusionOur findings demonstrate that, in breast cancer patients, Akt activation is associated with tumour proliferation and poor prognosis, particularly in the subset of patients with ErbB2-overexpressing tumours.

AbbreviationsCLISAchemiluminescence-linked immunoassay

DFSdisease-free survival

EIAenzyme immunoassay

ERoestrogen receptor

P-Aktphosphorylated Akt

PgRprogesterone receptor

PIP3phosphoinositol-3-phosphate

PKBprotein kinase B

RT-PCRreverse transcription polymerase chain reaction

STBStiftung Tumorbank Basel.

Electronic supplementary materialThe online version of this article doi:10.1186-bcr1015 contains supplementary material, which is available to authorized users.

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Autor: Jonas Cicenas - Patrick Urban - Vincent Vuaroqueaux - Martin Labuhn - Willy Küng - Edward Wight - Mark Mayhew - Urs Eppen

Fuente: https://link.springer.com/



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