title: 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.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.forename: Tingwei
authors.initials: T
authors.lastname: Su
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: Yiran
authors.initials: Y
authors.lastname: Jiang
authors.forename: Wenqi
authors.initials: W
authors.lastname: Yuan
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D020869:Gene Expression Profiling; D018734:Genes, erbB-2; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010235:Paraganglioma / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D010673:Pheochromocytoma / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases