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Different levels of various glucocorticoid-regulated genes in corticotroph adenomas.
MedLine Citation:
PMID:  23315031     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Recently, correlations between corticotroph tumor dedifferentiation and both E-cadherin immunostaining and reduced mRNA expression of the E-cadherin gene (CDH1) have been demonstrated. The purpose of this study was to explore whether tumor dedifferentiation correlated with glucocorticoid resistance and whether the resistance was associated with both positively and negatively regulated genes. Tumor material from 20 patients with verified Cushing's disease or Nelson's syndrome operated on at Rikshospitalet, Oslo. Reverse transcription polymerase chain reaction analysis of genes such as E-cadherin (CDH1), proopiomelanocortin (POMC), glucocorticoid-induced leucine zipper (GILZ), and thioredoxin-interacting protein (TXNIP) was performed. The correlations between the expression of the GILZ, TXNIP, and POMC genes in different stages of corticotroph adenomas, the E-cadherin mRNA expression and staining pattern, and the preoperative 24-h cortisol excretion were examined. The GILZ and TXNIP expression levels were positively correlated to the CDH1 expression and were highest in microadenomas and in tumors with a high membranous E-cadherin reactivity. In contrast, the POMC expression was not significantly different between the groups. This divergence between the genes that were positively and negatively regulated by glucocorticoids could not be supported by other gene expression analyses. No correlations to urinary cortisol were found. The expression of the glucocorticoid-responsive genes POMC, GILZ, and TXNIP in corticotroph adenomas showed a remarkable variation. The pattern and variability of glucocorticoid resistance in corticotroph adenomas seem to correlate with a loss of the epithelial phenotype associated with corticotroph tumor dedifferentiation.
Authors:
Johan Arild Evang; Jens Bollerslev; Olivera Casar-Borota; Tove Lekva; Jon Ramm-Pettersen; Jens Petter Berg
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-13
Journal Detail:
Title:  Endocrine     Volume:  -     ISSN:  1559-0100     ISO Abbreviation:  Endocrine     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9434444     Medline TA:  Endocrine     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Section of Specialized Endocrinology, Oslo University Hospital Rikshospitalet, P.O. Box 4950, Nydalen, 0424, Oslo, Norway, arild.evang@medisin.uio.no.
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