Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness Between African Americans and European Americans

Overview

Journal Cancer Epidemiol Biomarkers Prev

Specialties Biochemistry
Oncology
Public Health

Date 2021 Feb 23

PMID 33619025

Citations 3

Authors

Li Tang

Qianqian Zhu

Zinian Wang

Clayton M Shanahan

Jeannette T Bensen

Elizabeth T H Fontham

Gary J Smith

Elena A Pop

Gissou Azabdaftari

James L Mohler

Yue Wu

Affiliations

Soon will be listed here.

Abstract

Background: Androgen receptor signaling is crucial to prostate cancer aggressiveness. Members of the solute carrier family of the organic anion transporting peptides (SLCO) are potential regulators of androgen availability in prostate tissue. It remains unknown whether genetic variations in SLCOs contribute to the differences in prostate cancer aggressiveness in African Americans (AA) and European Americans (EA).

Methods: SNPs in 11 SLCO members were selected, with addition of 139 potentially functional SNPs and 128 ancestry informative markers. A total of 1,045 SNPs were genotyped and analyzed in 993 AAs and 1,057 EAs from the North Carolina-Louisiana Prostate Cancer Project. Expression and cellular localization of SLCOs were examined using qRT-PCR, IHC, and RNA hybridization in independent sets of prostate cancer cases.

Results: Significant associations with prostate cancer characteristics were found for SNPs in and . The associations differed by race ( < 0.05). SNPs in were associated with reduced tumor aggressiveness and low Gleason score in AAs; whereas, SNPs in were associated with high clinical stage in EAs. In prostate tissue, SLCO2A1 and SLCO5A1 were the most expressed SLCOs at the mRNA level and were expressed predominantly in prostate endothelial and epithelial cells at the protein level, respectively.

Conclusions: SLCO2A1 and SLCO5A1 play important but different roles in prostate cancer aggressiveness in AAs versus EAs.

Impact: The finding calls for consideration of racial differences in biomarker studies of prostate cancer and for investigations on functions of SLCO2A1 and SLCO5A1 in prostate cancer.

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References

Sharifi N, Hamada A, Sissung T, Danesi R, Venzon D, Baum C . A polymorphism in a transporter of testosterone is a determinant of androgen independence in prostate cancer. BJU Int. 2008; 102(5):617-21. PMC: 2574946. DOI: 10.1111/j.1464-410X.2008.07629.x. View

Heinlein C, Chang C . Androgen receptor in prostate cancer. Endocr Rev. 2004; 25(2):276-308. DOI: 10.1210/er.2002-0032. View

Mohler J, Gaston K, Moore D, Schell M, Cohen B, Weaver C . Racial differences in prostate androgen levels in men with clinically localized prostate cancer. J Urol. 2004; 171(6 Pt 1):2277-80. DOI: 10.1097/01.ju.0000127739.88383.79. View

Wright J, Kwon E, Ostrander E, Montgomery R, Lin D, Vessella R . Expression of SLCO transport genes in castration-resistant prostate cancer and impact of genetic variation in SLCO1B3 and SLCO2B1 on prostate cancer outcomes. Cancer Epidemiol Biomarkers Prev. 2011; 20(4):619-27. PMC: 3073610. DOI: 10.1158/1055-9965.EPI-10-1023. View

Auton A, Brooks L, Durbin R, Garrison E, Kang H, Korbel J . A global reference for human genetic variation. Nature. 2015; 526(7571):68-74. PMC: 4750478. DOI: 10.1038/nature15393. View

Cooper D . Functional intronic polymorphisms: Buried treasure awaiting discovery within our genes. Hum Genomics. 2010; 4(5):284-8. PMC: 3500160. DOI: 10.1186/1479-7364-4-5-284. View

Lee H, Leake B, Teft W, Tirona R, Kim R, Ho R . Contribution of hepatic organic anion-transporting polypeptides to docetaxel uptake and clearance. Mol Cancer Ther. 2015; 14(4):994-1003. PMC: 4394048. DOI: 10.1158/1535-7163.MCT-14-0547. View

Kanai N, Lu R, Satriano J, Bao Y, Wolkoff A, Schuster V . Identification and characterization of a prostaglandin transporter. Science. 1995; 268(5212):866-9. DOI: 10.1126/science.7754369. View

Nakanishi T, Ohno Y, Aotani R, Maruyama S, Shimada H, Kamo S . A novel role for OATP2A1/SLCO2A1 in a murine model of colon cancer. Sci Rep. 2017; 7(1):16567. PMC: 5707394. DOI: 10.1038/s41598-017-16738-y. View

10.

Yang M, Xie W, Mostaghel E, Nakabayashi M, Werner L, Sun T . SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer. J Clin Oncol. 2011; 29(18):2565-73. PMC: 3138634. DOI: 10.1200/JCO.2010.31.2405. View

11.

Mohler J . A role for the androgen-receptor in clinically localized and advanced prostate cancer. Best Pract Res Clin Endocrinol Metab. 2008; 22(2):357-72. PMC: 2799036. DOI: 10.1016/j.beem.2008.01.009. View

12.

de Morree E, Bottcher R, van Soest R, Aghai A, de Ridder C, Gibson A . Loss of SLCO1B3 drives taxane resistance in prostate cancer. Br J Cancer. 2016; 115(6):674-81. PMC: 5023781. DOI: 10.1038/bjc.2016.251. View

13.

Millar D, Horan M, Chuzhanova N, Cooper D . Characterisation of a functional intronic polymorphism in the human growth hormone (GH1) gene. Hum Genomics. 2010; 4(5):289-301. PMC: 3500161. DOI: 10.1186/1479-7364-4-5-289. View

14.

Pressler H, Sissung T, Venzon D, Price D, Figg W . Expression of OATP family members in hormone-related cancers: potential markers of progression. PLoS One. 2011; 6(5):e20372. PMC: 3098289. DOI: 10.1371/journal.pone.0020372. View

15.

Topper J, Cai J, Stavrakis G, Anderson K, Woolf E, Sampson B . Human prostaglandin transporter gene (hPGT) is regulated by fluid mechanical stimuli in cultured endothelial cells and expressed in vascular endothelium in vivo. Circulation. 1998; 98(22):2396-403. DOI: 10.1161/01.cir.98.22.2396. View

16.

DAmico A, Whittington R, Malkowicz S, Schultz D, Schnall M, Tomaszewski J . Combined modality staging of prostate carcinoma and its utility in predicting pathologic stage and postoperative prostate specific antigen failure. Urology. 1997; 49(3A Suppl):23-30. DOI: 10.1016/s0090-4295(97)00165-9. View

17.

Obaidat A, Roth M, Hagenbuch B . The expression and function of organic anion transporting polypeptides in normal tissues and in cancer. Annu Rev Pharmacol Toxicol. 2011; 52:135-51. PMC: 3257355. DOI: 10.1146/annurev-pharmtox-010510-100556. View

18.

Nakanishi T, Tamai I . Roles of Organic Anion Transporting Polypeptide 2A1 (OATP2A1/SLCO2A1) in Regulating the Pathophysiological Actions of Prostaglandins. AAPS J. 2017; 20(1):13. DOI: 10.1208/s12248-017-0163-8. View

19.

Khuri N, Zur A, Wittwer M, Lin L, Yee S, Sali A . Computational Discovery and Experimental Validation of Inhibitors of the Human Intestinal Transporter OATP2B1. J Chem Inf Model. 2017; 57(6):1402-1413. DOI: 10.1021/acs.jcim.6b00720. View

20.

de Graan A, Lancaster C, Obaidat A, Hagenbuch B, Elens L, Friberg L . Influence of polymorphic OATP1B-type carriers on the disposition of docetaxel. Clin Cancer Res. 2012; 18(16):4433-40. PMC: 3464009. DOI: 10.1158/1078-0432.CCR-12-0761. View