Datasets used in ORD-023417: Identification of Androgen Receptor Modulators in a Prostate Cancer Cell Line Microarray Compendium. This dataset is associated with the following publication: Rooney, J., B. Chorley, N. Kleinstreuer, and C. Corton. Identification of Androgen Receptor Modulators in a Prostate Cancer Cell Line Microarray Compendium. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 166(1): 146-162, (2018).

The microarray experiments used in the study. This dataset is associated with the following publication: Hill, T., J. Rooney, J. Abedini, H. El-Masri, C. Wood, and J. Corton. Gene Expression Thresholds Derived From Short-term Exposures Identify Rat Liver Tumorigens. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 177(1): 41-59, (2020).

Microarray experiments used in the study. This dataset is associated with the following publication: Corton, J., T. Hill, J. Sutherland, J. Stevens, and J. Rooney. A Set of Six Gene Expression Biomarkers Identify Rat Liver Tumorigens in Short-Term Assays. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 177(1): 11-26, (2020).

DNA microarrays were used to examine the temporal program of gene expression following treatment of a human prostate cancer cell line with androgen. Significant changes in levels of transcripts of more than 500 genes were observed; most were not previously known to be regulated by androgens.

Background Breast cancer is hormone related, as are cancers of the endometrium, ovary, and prostate. Several studies have suggested that higher extracellular levels of androgens are associated with breast cancer risk, while biological evidence indicates that androgens are protective. The codon 49 alanine to threonine substitution (A49T), codon 89 valine to leucine substitution (V89L) and TA repeat polymorphisms of the steroid 5α-reductase type II (SRD5A2) gene are considered functional with respect to enzyme activity converting testosterone into dihydrotestosterone. To test the hypothesis that these three polymorphisms are associated with risk of breast cancer, a case–control study was conducted with patients of Aichi Cancer Center Hospital. Methods The cases were 237 patients histologically diagnosed with breast cancer, and the controls were 185 noncancer outpatients. DNA from peripheral blood was genotyped by PCR methods. Results The threonine allele of A49T was not found in our subjects. Compared with the V/V genotype of V89L, the L/L genotype was associated with a decreased risk (crude odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.36–1.05). This was also the case for the TA(9/9) genotype, with an OR of 0.58 (95% CI = 0.13–2.63) relative to TA(0/0). Among women with the TA(0/0) genotype, however, the OR for the L/L genotype was 0.46 (95% CI = 0.24–0.88) compared with the V/V genotype, and those with the V/V and TA(0/0) genotypes had the highest risk. The haplotype with the L and TA(9) repeat alleles was not found. Conclusion This study is the first to our knowledge focusing on Japanese women, suggesting that SRD5A2 polymorphisms might have an association with breast cancer risk. Further large-sample studies will be required to confirm the association and to assess any interactions with environmental factors.

The links provided include the DrugMatrix-Affymetrix study, the TG-GATES study, and the TempO-Seq S1500+ study. This dataset is associated with the following publication: Lewis, R., T. Hill III, and C. Corton. A set of six Gene expression biomarkers and their thresholds identify rat liver tumorigens in short-term assays. TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 443: 152547, (2020).

Accession numbers for microarray datasets used in Oshida et al. Chemical and Hormonal Effects on STAT5b-Dependent Sexual Dimorphism of the Liver Transcriptome. PLoS One. 2016 Mar 9;11(3):e0150284. This dataset is associated with the following publication: Oshida, K., D. Waxman, and C. Corton. Chemical and Hormonal Effects on STAT5b-Dependent Sexual Dimorphism of the Liver Transcriptome.. PLoS ONE. Public Library of Science, San Francisco, CA, USA, 11(3): NA, (2016).

Microarray experiments examined in the study. This dataset is associated with the following publication: Rooney, J., N. Ryan, J. Liu, R. Houtman, R. van Beuningen, J. Hsieh, G. Chang, S. Chen, and J. Corton. A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor α in an MCF-7 Microarray Compendium. CHEMICAL RESEARCH IN TOXICOLOGY. American Chemical Society, Washington, DC, USA, 34(2): 313-329, (2021).

Data was generated at KUMC, not EPA. There is no EPA data that is part of this submission. This dataset is associated with the following publication: Liu, J., J.Y. Cui, Y. Lu, C. Corton, and C. Klaassen. Sex-, Age-, and Race/Ethnicity-Dependent Variations in Drug-Processing and NRF2-Regulated Genes in Human Livers. DRUG METABOLISM AND DISPOSITION. American Society for Pharmacology and Experimental Therapeutics, Bethesda, MD, USA, 49(1): 111-119, (2021).

Background Modulation of the expression of retinoic acid receptors (RAR) α and γ in adult rat prostate by testosterone (T) suggests that RAR signaling events might mediate some of the androgen effects on prostate cells. Method In this study, we examined the interactions between T and retinoic acid (RA) in cell growth of human prostate carcinoma cells, LNCaP, and their relationship with the expression of RAR and epidermal growth factor receptor (EGF-R). Results Both T and RA, when administered alone, stimulated 3H-thymidine incorporation in LNCaP cells in a dose-dependent manner; the effect of each agent was reciprocally attenuated by the other agent. Testosterone treatment of LNCaP cells also resulted in dose dependent, biphasic increases in RAR α and γ mRNAs; increases paralleled that of 3H-thymidine incorporation and were attenuated by the presence of 100 nM RA. These results suggest a link between RAR signaling and the effect of T on LNCaP cell growth. Gel electrophoretic mobility shift assays revealed the presence of putative androgen responsive element (ARE) in the promoter region of RAR α gene, suggesting that a direct AR-DNA interaction might mediate the effects of T on RAR α gene. Furthermore, treatment of LNCaP cells with 20 nM T resulted in an increase in EGF-R. In contrast, EGF-R was suppressed by 100 nM RA that also suppressed the effect of T. Conclusions Current results demonstrate interactions between T and RA in the expression of RARs and cell growth in LNCaP cells. The presence of putative ARE in the promoter of the RAR α gene suggests that AR-DNA interaction might mediate the effects of T on RAR α gene. The opposite effects of T and RA on the expression of RAR and EGF-R suggest that signal events of these receptors might be involved in the interaction between T and RA in the control of LNCaP cell growth.