TY - JOUR
T1 - Development and pre-validation of an in vitro transactivation assay for detection of (anti)androgenic potential compounds using 22Rv1/MMTV cells
AU - Sun, Seunghan
AU - Park, Eun Jung
AU - Choi, Yun Ho
AU - Lee, Hee Seok
AU - Ahn, Byung Yoon
AU - Dong, Mi Sook
N1 - Funding Information:
This research was supported by a grant ( 11161MFDS728 , 12161MFDS737 , and 13162MFDS803 ) from the Ministry of Food and Drug Safety awarded from 2011 to 2013 and by a Korea University Grant.
Publisher Copyright:
© 2016 Elsevier Inc.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - 22Rv1/MMTV cell line
KW - Androgen receptor-mediated transcriptional activation assay
KW - Androgenic and anti-androgenic endocrine disruptors
KW - Endocrine disruptor screening
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U2 - 10.1016/j.reprotox.2016.02.006
DO - 10.1016/j.reprotox.2016.02.006
M3 - Article
C2 - 26867867
AN - SCOPUS:84961215719
SN - 0890-6238
VL - 60
SP - 156
EP - 166
JO - Reproductigve Toxicoloy
JF - Reproductigve Toxicoloy
ER -
