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This Article Accepted manuscript (PDF) All Versions of this Article: ERC-08-0003v1 ERC-08-0003v2 15/4/1099    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ribeiro-Oliveira, A. Articles by Korbonits, M. PubMed PubMed Citation Articles by Ribeiro-Oliveira, A. Articles by Korbonits, M.

A Ribeiro-Oliveira, Barts and The London, London, EC1M 6BQ, United Kingdom
G Franchi, Endocrinology, Barts and The London, London, United Kingdom
B Kola, Endocrinology, Barts and The London, London, United Kingdom
P Dalino, Endocrinology, Barts and The London, London, United Kingdom
S Pinheiro, Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil
N Salahuddin, London, United Kingdom
M Musat, London, United Kingdom
M Goth, Internal Medicine, National Medical Center, Budapest, Hungary
S Czirjak, Neurosurgery, National Institute of Neurosurgery, Budapest, Hungary
Z Hanzely, Neurosurgery, National Institute of Neurosurgery, Budapest, Hungary
D Silva, Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil
E Paulino, Federal University of Minas Gerais, Belo Horizonte, Brazil
A Grossman, Dept. of Endocrinology, St. Bartholomew's Hospital, London, United Kingdom
M Korbonits, Endocrinology, Barts and the London Medical School, London, United Kingdom

Correspondence: Antonio Ribeiro-Oliveira, Email: brolivei{at}uol.com.br

Abstract

The molecular analysis of pituitary tumours has received a great deal of attention, although the majority of studies have concentrated on the genome and the transcriptome. We aimed to study the proteome of human pituitary adenomas. A protein array using 1005 monoclonal antibodies was used to study growth hormone-, corticotrophin- and prolactin-secreting as well as non-functioning pituitary adenomas. Individual protein-expression levels in the tumours were compared to the expression profile of normal pituitary tissue. 316 proteins were detected in the pituitary tissue samples; of these, 116 proteins had not previously been described in human pituitary tissue. Four prominent differentially expressed proteins with potential importance to tumorigenesis were chosen for validation by immunohistochemistry and Western blotting. In the protein array analysis heat shock protein 110 (HSP110) and B2 bradykinin receptor were significantly over-expressed in all adenoma subtypes, while C-terminal src kinase (CSK) and annexin II were significantly under-expressed in all adenoma subtypes. The immunohistochemical analysis confirmed the over-expression of HSP110 and B2 bradykinin receptor and under-expression of CSK and annexin II in pituitary adenoma cells when compared to their corresponding normal pituitary cells. Western blotting only partially confirmed the proteomics data: HSP110 was significantly over-expressed in prolactinomas and non-functioning pituitary adenomas, the B2 bradykinin receptor was significantly over-expressed in prolactinomas, annexin II was significantly under-expressed in somatotrophinomas, while CSK did not show significant under-expression in any tumour. Protein expression analysis of pituitary samples disclosed both novel proteins and putative protein candidates for pituitary tumorigenesis, though validations using conventional techniques are necessary to confirm the protein expression data.