title: Development and pre-validation of an in vitro transactivation assay for detection of (anti)androgenic potential compounds using 22Rv1/MMTV cells.
abstract: The endocrine-disrupting effects of androgenic signaling play crucial roles in several androgen-related diseases. In attempting to develop an in vitro cell line to be used in androgen receptor (AR)-mediated reporter gene assays, we developed a stable 22Rv1/MMTV cell line, which is a human prostate cancer cell line that endogenously expresses functional AR, to evaluate AR-mediated transcriptional activation (TA). Using 22Rv1/MMTV cells, we established and optimized a test protocol for the AR-TA assay and validated the proposed assay using 20 compounds recommended by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). All the performance parameters for agonist and antagonist assays were 91-100% comparable between the 22Rv1/MMTV assay and the ICCVAM report. In conclusion, the AR-TA assay using 22Rv1/MMTV cells might be a quick and relatively inexpensive method for screening large numbers of chemicals for their potential to activate or inhibit AR-mediated gene transcription.
authors: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors: Seunghan
authors: S
authors: Sun
authors: Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do 363-700, Republic of Korea.
authors: Eun-Jung
authors: EJ
authors: Park
authors: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors: Yun-Ho
authors: YH
authors: Choi
authors: Food Safety Risk Assessment Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do 363-700, Republic of Korea.
authors: Hee-Seok
authors: HS
authors: Lee
authors: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors: Byung Yoon
authors: BY
authors: Ahn
authors: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. Electronic address: msdong@korea.ac.kr.
authors: Mi-Sook
authors: MS
authors: Dong
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D001681:Biological Assay; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D011944:Receptors, Androgen; D008156:Luciferases
keywords: 22Rv1/MMTV cell line; Androgen receptor-mediated transcriptional activation assay; Androgenic and anti-androgenic endocrine disruptors; Endocrine disruptor screening