title: Dual repressive effect of angiotensin II-type 1 receptor blocker telmisartan on angiotensin II-induced and estradiol-induced uterine leiomyoma cell proliferation.
abstract: BACKGROUND
  Although uterine leiomyomas or fibroids are the most common gynecological benign tumor and greatly affect reproductive health and well-being, the pathophysiology and epidemiology of uterine leiomyomas are poorly understood. Elevated blood pressure has an independent, positive association with risk for clinically detected uterine leiomyoma. Angiotensin II (Ang II) is a key biological peptide in the renin-angiotensin system that regulates blood pressure.
  
  
  METHODS
  In this study, we investigated the potential role of Ang II (1-1000 nM) in the proliferation of rat ELT-3 leiomyoma cells in vitro. RT-PCR and western blot analysis with cell proliferation and DNA transfection assays were performed to determine the mechanism of action of Ang II.
  
  
  RESULTS
  Ang II induced ELT-3 leiomyoma cell proliferation (P < 0.01) and the expression of Ang II type 1 receptor (AT(1)R) and AT(2)R mRNA and protein was confirmed. Regarding the intracellular signaling pathway, the Ang II-induced cell proliferation was AT(1)R-, epidermal growth factor receptor-, extracellular-regulated kinase- and protein kinase C-dependent but was not dependent on the AT(2)R or phosphatidylinositol-3 kinase or JAK kinase. The AT(1)R blocker telmisartan, effectively repressed Ang II-induced and estradiol-induced cell proliferation (P < 0.01). AT(1)R, but not AT(2)R, plays a role in Ang II-induced ELT-3 cell proliferation.
  
  
  CONCLUSIONS
  These experimental findings in vitro highlight the potential role of Ang II in the proliferation of leiomyoma cells.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Isobe
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakata
authors.forename: Asako
authors.initials: A
authors.lastname: Miyake
authors.forename: Toshiya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Ryoko
authors.initials: R
authors.lastname: Minekawa
authors.forename: Fumihito
authors.initials: F
authors.lastname: Nishimoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Oskamoto
authors.forename: Cheryl Lyn
authors.initials: CL
authors.lastname: Walker
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007889:Leiomyoma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D015398:Signal Transduction; D000077333:Telmisartan; D014594:Uterine Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D004958:Estradiol; D000077333:Telmisartan