Enhancement of androgen transcriptional activation assay based on genome edited glucocorticoid knock out human prostate cancer cell line

Hee Seok Lee; Seok Hee Lee; Yooheon Park

doi:10.1016/j.envres.2019.01.027

Enhancement of androgen transcriptional activation assay based on genome edited glucocorticoid knock out human prostate cancer cell line

Hee Seok Lee, Seok Hee Lee, Yooheon Park

Department of Food Science & Biotechnology

National Institute of Food and Drug Safety Evaluation

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Endocrine-disrupting chemicals (EDCs) interfere with the biological activity of hormones. Among EDC's, (anti-)androgenic compounds potentially cause several androgen-related diseases. To improve the accuracy of an in vitro transactivation assay (TA) for detection of (anti-)androgenic compounds, We established the glucocorticoid receptor (GR) knockout 22Rv1/MMTV cell line by using an RNA-guided engineered nuclease (RGEN)-derived CRISPR/Cas system. The 22Rv1/MMTV GRKO cell line was characterized and validated by androgen receptor (AR)-mediated TA assay compared with the AR-TA assay using 22Rv1/MMTV. In conclusion, the AR-TA assay with the 22Rv1/MMTV GRKO cell line was more accurate, excluding the misleading signals derived from glucocorticoids or equivalent chemicals, and might be an effective method for screening potential (anti-)androgenic compounds.

Original language	English
Pages (from-to)	437-443
Number of pages	7
Journal	Environmental Research
Volume	171
DOIs	https://doi.org/10.1016/j.envres.2019.01.027
State	Published - Apr 2019

Keywords

22Rv1 cell lines
Androgen transactivation assay
Glucocorticoid receptor
RNA-guided engineered nuclease

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.envres.2019.01.027

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title = "Enhancement of androgen transcriptional activation assay based on genome edited glucocorticoid knock out human prostate cancer cell line",

abstract = "Endocrine-disrupting chemicals (EDCs) interfere with the biological activity of hormones. Among EDC's, (anti-)androgenic compounds potentially cause several androgen-related diseases. To improve the accuracy of an in vitro transactivation assay (TA) for detection of (anti-)androgenic compounds, We established the glucocorticoid receptor (GR) knockout 22Rv1/MMTV cell line by using an RNA-guided engineered nuclease (RGEN)-derived CRISPR/Cas system. The 22Rv1/MMTV GRKO cell line was characterized and validated by androgen receptor (AR)-mediated TA assay compared with the AR-TA assay using 22Rv1/MMTV. In conclusion, the AR-TA assay with the 22Rv1/MMTV GRKO cell line was more accurate, excluding the misleading signals derived from glucocorticoids or equivalent chemicals, and might be an effective method for screening potential (anti-)androgenic compounds.",

keywords = "22Rv1 cell lines, Androgen transactivation assay, Glucocorticoid receptor, RNA-guided engineered nuclease",

author = "Lee, {Hee Seok} and Lee, {Seok Hee} and Yooheon Park",

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year = "2019",

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doi = "10.1016/j.envres.2019.01.027",

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T1 - Enhancement of androgen transcriptional activation assay based on genome edited glucocorticoid knock out human prostate cancer cell line

AU - Lee, Hee Seok

AU - Lee, Seok Hee

AU - Park, Yooheon

PY - 2019/4

Y1 - 2019/4

N2 - Endocrine-disrupting chemicals (EDCs) interfere with the biological activity of hormones. Among EDC's, (anti-)androgenic compounds potentially cause several androgen-related diseases. To improve the accuracy of an in vitro transactivation assay (TA) for detection of (anti-)androgenic compounds, We established the glucocorticoid receptor (GR) knockout 22Rv1/MMTV cell line by using an RNA-guided engineered nuclease (RGEN)-derived CRISPR/Cas system. The 22Rv1/MMTV GRKO cell line was characterized and validated by androgen receptor (AR)-mediated TA assay compared with the AR-TA assay using 22Rv1/MMTV. In conclusion, the AR-TA assay with the 22Rv1/MMTV GRKO cell line was more accurate, excluding the misleading signals derived from glucocorticoids or equivalent chemicals, and might be an effective method for screening potential (anti-)androgenic compounds.

AB - Endocrine-disrupting chemicals (EDCs) interfere with the biological activity of hormones. Among EDC's, (anti-)androgenic compounds potentially cause several androgen-related diseases. To improve the accuracy of an in vitro transactivation assay (TA) for detection of (anti-)androgenic compounds, We established the glucocorticoid receptor (GR) knockout 22Rv1/MMTV cell line by using an RNA-guided engineered nuclease (RGEN)-derived CRISPR/Cas system. The 22Rv1/MMTV GRKO cell line was characterized and validated by androgen receptor (AR)-mediated TA assay compared with the AR-TA assay using 22Rv1/MMTV. In conclusion, the AR-TA assay with the 22Rv1/MMTV GRKO cell line was more accurate, excluding the misleading signals derived from glucocorticoids or equivalent chemicals, and might be an effective method for screening potential (anti-)androgenic compounds.

KW - 22Rv1 cell lines

KW - Androgen transactivation assay

KW - Glucocorticoid receptor

KW - RNA-guided engineered nuclease

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SP - 437

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JO - Environmental Research

JF - Environmental Research

ER -

Enhancement of androgen transcriptional activation assay based on genome edited glucocorticoid knock out human prostate cancer cell line

Abstract

Keywords

UN SDGs

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