title: Retinoic Acid Receptor β: A Potential Therapeutic Target in Retinoic Acid Treatment of Endometrial Cancer.
abstract: Several studies have reported that retinoic acid (RA) might be used to treat malignancies. The effects of RA are mediated by the RA receptor (RAR), and RARα/RARβ especially acts as a tumor suppressor. However, little is known about its role in human endometrial cancer.
  
  
  
  In this study, we examined the effects of all-trans RA (ATRA) on progression of human endometrial cancer cell line, RL95-2 and Hec1A. We then examined the expression of RARα and RARβ in 50 endometrial cancer tissues by using immunohistochemistry.
  
  
  
  We found inhibitory effects of ATRA on cell proliferation, apoptosis, and migration in RL95-2 cells, but not in Hec1A cells. RARα or RARβ knockdown individually could not cancel out the inhibition of cell proliferation by ATRA in RL95-2 cells, but simultaneous knockdown of RARα and RARβ could block its effect on proliferation. RARα and RARβ knockdown dose dependently reduced the inhibition of migration by ATRA, but the effect was more pronounced with RARβ knockdown than with RARα knockdown. We confirmed that RARβ gene was directly regulated by ATRA in microarray and real-time reverse transcription polymerase chain reaction. Furthermore, the RARβ agonist (BMS453) significantly suppressed proliferation of RL95-2 cells. In immunohistochemical analysis, RARα expression was positively correlated with tumor grade, and RARβ showed the opposite tendency in endometrial cancer.
  
  
  
  Retinoic acid might have multiple antitumor effects, and RARβ may be a potent therapeutic target in RA treatment for endometrial cancers.
authors.affiliation: *Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine; †Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science, Tohoku University; and ‡Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Tsuji
authors.forename: Hiroki
authors.initials: H
authors.lastname: Utsunomiya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Mayu
authors.initials: M
authors.lastname: Hanihara
authors.forename: Misaki
authors.initials: M
authors.lastname: Fue
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takagi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nishimoto
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Suzuki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ito
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D058990:Molecular Targeted Therapy; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C082925:retinoic acid receptor beta; D014212:Tretinoin