RRC ID 65685
著者 Tsuji K, Utsunomiya H, Miki Y, Hanihara M, Fue M, Takagi K, Nishimoto M, Suzuki F, Yaegashi N, Suzuki T, Ito K.
タイトル Retinoic Acid Receptor β: A Potential Therapeutic Target in Retinoic Acid Treatment of Endometrial Cancer.
ジャーナル Int J Gynecol Cancer
Abstract OBJECTIVE: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.
MATERIALS AND METHODS: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.
RESULTS: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.
CONCLUSIONS:Retinoic acid might have multiple antitumor effects, and RARβ may be a potent therapeutic target in RA treatment for endometrial cancers.
巻・号 27(4)
ページ 643-650
公開日 2017-5-1
DOI 10.1097/IGC.0000000000000995
PMID 28375930
MeSH Cell Line, Tumor Cell Movement / drug effects Cell Survival / drug effects Endometrial Neoplasms / drug therapy* Endometrial Neoplasms / genetics Endometrial Neoplasms / metabolism Endometrial Neoplasms / pathology Female Gene Knockdown Techniques Humans Immunohistochemistry Molecular Targeted Therapy Receptors, Retinoic Acid / biosynthesis Receptors, Retinoic Acid / deficiency Receptors, Retinoic Acid / genetics Receptors, Retinoic Acid / metabolism* Retinoic Acid Receptor alpha / biosynthesis Retinoic Acid Receptor alpha / deficiency Retinoic Acid Receptor alpha / genetics Retinoic Acid Receptor alpha / metabolism Tretinoin / pharmacology*
IF 2.095
リソース情報
ヒト・動物細胞 Sawano(RCB1152)