title: Comparison of prostate cancer cell lines for androgen receptor-mediated reporter gene assays.
abstract: In order to select a better prostate cancer cell model for androgen receptor (AR)-mediated reporter gene assays, we assessed the androgen response characteristics of three cell lines, LNCaP, PC3/AR(+) and 22Rv1, in this study. Both the mRNA and the proteins of AR and glucocorticoid receptor (GR) were expressed in all three cell lines. Among the three cell lines, only in LNCaP cells, DHT concentration-dependently stimulated proliferation. DHT induced the luciferase activity in three cell lines which were transiently transfected with pMMTV-Luc, in a concentration-dependent manner. The maximum induction was 24.0-fold and 13.4-fold in 22Rv1 and in the LNCaP respectively. PC3/AR(+) were more sensitive to respond to DHT at a minimal concentration of 10(-12)M by 14.0-fold induction. The transcriptional activity induced with 10(-8)M DHT was inhibited about 50-75% in the PC3/AR(+) and 22Rv1, and 98% in the LNCaP, by vinclozolin. Dexamethasone concentration-dependently induced the luciferase activity in PC3 and 22Rv1, but not in the LNCaP. However, the response to dexamethasone in 22Rv1 was very weak compared to DHT. The (anti)androgencity of seven pyrethroids was assessed via an AR-mediated luciferase reporter assay. None of them showed the androgenic action in all three cell lines. Permethrin inhibited the DHT induced luciferase activity about 22%, 35.8% and 75.5% in 22Rv1, PC3/AR(+) and LNCaP, respectively. Based on results from in this study and cell line character, 22Rv1 cells seemed to be an appropriate model for the screening of androgenic endocrine disruptors, although it needs further studies with other steroid receptor and thyroid receptor.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, 1, 5-Ka, Anam-dong, Sungbuk-ku, Seoul 136-701, Republic of Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young In
authors.initials: YI
authors.lastname: Park
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Dong
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D007306:Insecticides / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010080:Oxazoles / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011722:Pyrethrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000726:Androgen Antagonists; D005659:Fungicides, Industrial; D007306:Insecticides; D010080:Oxazoles; D011722:Pyrethrins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011965:Receptors, Glucocorticoid; D011993:Recombinant Fusion Proteins; C411470:glucocorticoid receptor alpha; D013196:Dihydrotestosterone; D003907:Dexamethasone; D008156:Luciferases; C025643:vinclozolin