Gene expression profiles of phaeochromocytomas with ERBB2 overexpression reveal a new molecular mechanism tumourigenicity.

Abstract:

OBJECTIVE:Phaeochromocytomas (PHEO) and functional paragangliomas (PGLs) are catecholamine-secreting neuroendocrine tumours. Although most PHEO/PGLs are benign, 10-35% present as (or develop into) malignant tumours with a poor prognosis. Overexpression of ERBB2 (v-erb-b2 erythroblastic leukaemia viral oncogene homologue 2) has been reported to be associated with malignant PHEO. We used gene expression profiling of PHEO/PGLs to gain a better understanding of the tumourigenic pathways associated with ERBB2. METHODS:We used the Affymetrix Gene Chip U133 Plus 2·0 genome-wide gene expression cDNA microarray of 18 PHEO/PGLs (12 benign and six malignant, divided into two groups depending on ERBB2 expression levels) to analyse the gene expression patterns. RESULTS:Unsupervised hierarchical cluster analysis of transcription profiles of 18 samples identified two dominant expression clusters corresponding to samples belonging to the ERBB2+ and ERBB2- groups. According to the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases, the differentially expressed genes were classified into diverse functional categories and signalling pathways. In particular, the focal adhesion signalling pathway showed significant differences between the groups; specifically, the FAK-Src-MAPK pathway was prominently activated in the ERBB2+ group. CONCLUSIONS:In summary, ERBB2+ PHEO/PGLs have a distinct expression pattern compared with the ERBB2- group. The focal adhesion signalling pathway may participate in ERBB2-induced tumourigenesis in PHEO/PGLs.

journal_name

Clin Endocrinol (Oxf)

journal_title

Clinical endocrinology

authors

Qi Y,Su T,Zhang X,Jiang Y,Yuan W,Wang W,Cui B,Ning G

doi

10.1111/j.1365-2265.2012.04388.x

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

399-406

issue

3

eissn

0300-0664

issn

1365-2265

journal_volume

77

pub_type

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