title: Early growth response-2 expression in uterine leiomyoma cells: regulation and function.
abstract: OBJECTIVE
  To investigate the regulation of early growth response-2 (Egr-2) by transforming growth factor β3 (TGF-β3) and its functions in cultured human uterine leiomyoma smooth muscle cells.
  
  
  METHODS
  Laboratory research.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Primary leiomyoma cells from patients with symptomatic leiomyomata.
  
  
  METHODS
  Tissue culture followed by RNA and protein analysis.
  
  
  METHODS
  Cell proliferation, alteration in extracellular matrix component expression.
  
  
  RESULTS
  In vivo mRNA levels of Egr-2 were statistically significantly higher in leiomyoma tissues compared with matched myometrial tissues, and showed a statistically significant correlation with TGF-β3 messenger RNA (mRNA) levels in leiomyoma tissues. In primary leiomyoma smooth muscle cells, TGF-β3 statistically significantly induced Egr-2 gene expression in a dose-dependent and time-dependent manner. Small interfering RNA (siRNA) knockdown of Egr-2 markedly increased the level of the proliferation marker proliferating cell nuclear antigen and the expression of proto-oncogene c-myc. On the other hand, ablation of Egr-2 stimulated collagen-1A1 and collagen-3A1 transcription and inhibited dermatopontin gene expression. However, the mRNA levels of α-smooth muscle actin and fibronectin were not affected by Egr-2 knockdown.
  
  
  CONCLUSIONS
  We demonstrated that TGF-β3 regulated Egr-2 gene expression and presented evidence that Egr-2 decreases collagen production and stimulates dermatopontin gene expression.
authors.affiliation: Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Yin
authors.forename: Antonia
authors.initials: A
authors.lastname: Navarro
authors.forename: Feng
authors.initials: F
authors.lastname: Fang
authors.forename: Anna
authors.initials: A
authors.lastname: Xie
authors.forename: John S
authors.initials: JS
authors.lastname: Coon
authors.forename: Carrie
authors.initials: C
authors.lastname: Richardson
authors.forename: Serdar E
authors.initials: SE
authors.lastname: Bulun
mesh_terms: D000199:Actins / Q000235:genetics; D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D049109:Cell Proliferation; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000235:genetics; D051767:Early Growth Response Protein 2 / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C439971:COL3A1 protein, human; D011508:Chondroitin Sulfate Proteoglycans; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; C082019:DPT protein, human; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; C000715470:MAS1 protein, human; C489427:MYC protein, human; D018809:Proliferating Cell Nuclear Antigen; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C509044:TGFB3 protein, human; D053782:Transforming Growth Factor beta3