title: Different levels of various glucocorticoid-regulated genes in corticotroph adenomas.
abstract: 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: Section of Specialized Endocrinology, Oslo University Hospital Rikshospitalet, P.O. Box 4950, Nydalen, 0424, Oslo, Norway. arild.evang@medisin.uio.no
authors: Johan Arild
authors: JA
authors: Evang
authors: Jens
authors: J
authors: Bollerslev
authors: Olivera
authors: O
authors: Casar-Borota
authors: Tove
authors: T
authors: Lekva
authors: Jon
authors: J
authors: Ramm-Pettersen
authors: Jens Petter
authors: JP
authors: Berg
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000235:genetics* / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D052138:Genes, Neoplasm / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D005938:Glucocorticoids; D012333:RNA, Messenger; C404226:TSC22D3 protein, human; C486715:TXNIP protein, human; D014157:Transcription Factors; D011333:Pro-Opiomelanocortin