Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma

Revill, K., Dudley, K. J., Clayton, R. N., McNicol, A.M. and Farrell, W. E. (2009) Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma. Endocrine - Related Cancer, 16 2: 537-548. doi:10.1677/ERC-09-0008


Author Revill, K.
Dudley, K. J.
Clayton, R. N.
McNicol, A.M.
Farrell, W. E.
Title Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma
Journal name Endocrine - Related Cancer   Check publisher's open access policy
ISSN 1351-0088
1479-6821
Publication date 2009-06-01
Sub-type Article (original research)
DOI 10.1677/ERC-09-0008
Open Access Status Not yet assessed
Volume 16
Issue 2
Start page 537
End page 548
Total pages 12
Place of publication Bristol, U.K.
Publisher BioScientifica
Language eng
Abstract The imprinted gene, neuronatin (NNAT), is one of the most abundant transcripts in the pituitary and is thought to be involved in the development and maturation of this gland. In a recent whole-genome approach, exploiting a pituitary tumour cell line, we identified hypermethylation associated loss of NNAT. In this report, we determined the expression pattern of NNAT in individual cell types of the normal gland and within each of the different pituitary adenoma subtypes. In addition, we determined associations between expression and CpG island methylation and used colony forming efficiency assays (CFE) to gain further insight into the tumour-suppressor function of this gene. Immunohistochemical (IHC) co-localization studies of normal pituitaries showed that each of the hormone secreting cells (GH, PRL, ACTH, FSH and TSH) expressed NNAT. However, 33 out of 47 adenomas comprising, 11 somatotrophinomas, 10 prolactinomas, 12 corticotrophinomas and 14 non-functioning tumours, irrespective of subtype failed to express either NNAT transcript or protein as determined by quantitative real-time RT-PCR and IHC respectively. In normal pituitaries and adenomas that expressed NNAT the promoter-associated CpG island showed characteristics of an imprinted gene where w50% of molecules were densely methylated. However, in the majority of adenomas that showed loss or significantly reduced expression of NNAT, relative to normal pituitaries, the gene-associated CpG island showed ignificantly increased methylation. Induced expression of NNAT in transfected AtT-20 cells significantly reduced CFE. Collectively, these findings point to an important role for NNAT in the pituitary and perhaps tumour development in this gland.
Keyword Genome-wide analysis
Gene-expression
Suppressor genes
Tumour
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 24 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 24 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 27 Dec 2009, 10:03:51 EST