title: Different effects of epidermal growth factor on smooth muscle cells derived from human myometrium and from leiomyoma.
abstract: OBJECTIVE
  To determine different effects of epidermal growth factor (EGF) on cultured smooth muscle cells (SMCs) derived from human myometrium and leiomyoma.
  
  
  METHODS
  EGF effects on DNA synthesis and intracellular signal transduction were studied in cultured SMCs from leiomyoma and its matched myometrium.
  
  
  METHODS
  Research laboratories.
  
  
  METHODS
  Patients 35-50 years old with uterine leiomyomas.
  
  
  METHODS
  Hysterectomy.
  
  
  METHODS
  Signal transduction from EGF receptor.
  
  
  RESULTS
  As analyzed by laser scanning cytometry (LSC), EGF treatment stimulated DNA synthesis and induced polyploidization of leiomyomal, but not myometrial, SMCs. EGF stimulation was inhibited by AG1478, an EGF receptor (EGFR) inhibitor and PD98059, a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor. Both leiomyomal and myometrial SMCs had similar expression levels of EGFR, but EGF treatment induced transient phosphorylation activation of EGFR and Akt in leiomyomal SMCs. Consequently, EGF triggered transient phosphorylation activation of p44/42 MAPK in leiomyomal SMCs, followed by down-regulation of p27. In myometrial SMCs, however, EGF induced sustained activation of EGFR, Akt, and p44/42 MAPK with up-regulation of p27.
  
  
  CONCLUSIONS
  EGF stimulates DNA synthesis and polyploidization in leiomyomal SMCs through transient activation of the EGFR-MAPK pathway. Given that polyploidization plays a role in tumorigenesis, our results shed new light on the pathogenesis of human uterine leiomyoma.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nankai University School of Medicine, Tianjin, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ren
authors.forename: Hao
authors.initials: H
authors.lastname: Yin
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Tian
authors.forename: Lihua
authors.initials: L
authors.lastname: Cui
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Wanjun
authors.initials: W
authors.lastname: Lin
authors.forename: Xiang D
authors.initials: XD
authors.lastname: Tang
authors.forename: Yu
authors.initials: Y
authors.lastname: Gui
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D011123:Polyploidy
chemical_list: D004815:Epidermal Growth Factor