title: Gene expression profiling identifies ESRP1 as a potential regulator of epithelial mesenchymal transition in somatotroph adenomas from a large cohort of patients with acromegaly.
abstract: BACKGROUND
  The epithelial marker E-cadherin plays a crucial role in epithelial-mesenchymal transition (EMT). Decreased protein content in somatotroph adenomas has been associated with increased tumor size, invasion, and poor response to somatostatin analog (SA) treatment, but the potential mechanisms of EMT progression in these adenomas are lacking.
  
  
  OBJECTIVE
  We hypothesized that characterization of EMT-related transcripts in somatotroph adenomas could identify novel therapeutic targets in individuals with poor response to SA treatment and provide more knowledge of the mechanism of EMT progression.
  
  
  METHODS
  Fifty-three patients with acromegaly participated in the study.
  
  
  METHODS
  We performed microarray analysis of 16 adenomas, eight with high expression and eight with low expression of E-cadherin, in order to identify EMT-related transcripts. Candidate transcripts were further explored in vivo in 53 adenomas and in vitro in a rat pituitary GH-producing cell (GH3) after exploring three models for reducing E-cadherin and inducing a mesenchymal phenotype.
  
  
  RESULTS
  In vivo E-cadherin mRNA expression in tumor tissue is associated negatively with tumor size and invasiveness and positively with GH and IGF-I levels in serum and response to SA treatment. Microarray and subsequent PCR analysis identify several EMT-related genes associated with E-cadherin expression. In vitro, few of these EMT-related genes were regulated by silencing E-cadherin or by TGF-β1 treatment in GH3 cells. In contrast, silencing Esrp1 in GH3 cells regulated many of the EMT-related transcripts.
  
  
  CONCLUSIONS
  These results indicate that ESRP1 could be a master regulator of the EMT process in pituitary adenomas causing acromegaly.
authors.affiliation: Section of Specialized Endocrinology, Department of Endocrinology, and Research Institute for Internal Medicine, Oslo University Hospital, 0424 Oslo, Norway. tove.lekva@medisin.uio.no
authors.forename: Tove
authors.initials: T
authors.lastname: Lekva
authors.forename: Jens Petter
authors.initials: JP
authors.lastname: Berg
authors.forename: Stine Lyngvi
authors.initials: SL
authors.lastname: Fougner
authors.forename: Ole Kristoffer
authors.initials: OK
authors.lastname: Olstad
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Jens
authors.initials: J
authors.lastname: Bollerslev
mesh_terms: D000172:Acromegaly / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D015331:Cohort Studies; D058750:Epithelial-Mesenchymal Transition; D020869:Gene Expression Profiling; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015820:Cadherins; C539364:ESRP1 protein, human; D016601:RNA-Binding Proteins