Effect of SLC01B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-Lndependent prostatic cancer

Akinobu Hamada, Tristan Sissung, Douglas K. Price, Romano Danesi, Cindy H. Chau, Nima Sharifi, David Venzon, Kenji Maeda, Keisuke Nagao, Alex Sparreboom, Hiroaki Mitsuya, William L. Dahut, William D. Figg

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Abstract

Purpose: The organic anion transporter 0ATP1B3, encoded by SLC01B3, is involved in the transport of steroid hormones. However, its role in testosterone uptake and clinical outcome of prostatic cancer is unknown. This study examined (a) the SLC01B3 genotype in cancer cells as well as the uptake of testosterone by cells transfected with genetic variants of SLC01B3; (b) the expression of 0ATP163 in normal prostate, benign prostatic hyperplasia, and prostatic cancer; and (c) the role of SLC01B3 haplotype on clinical outcome of Caucasian patients with androgen-independent prostatic cancer. Experimental Design: SLC01B3 genotype was assessed in the NCI-60 panel of tumor cells by sequencing, whereas testosterone transport was analyzed in Cos-7 cells transfected with WT, 334G, and 699A SLC01B3 variants. 0ATP1B3 expression in prostatic tissues was examined by fluorescence microscopy, and the relationship between SLC01B3 haplotypes and survival was examined in patients. Results: Cells transfected with wild-type (334T/699G) SLC01B3, or with a vector containing either the 334G or 699A variants, actively transported testosterone, whereas its uptake was impaired in cells transfected with a gene carrying both 334G and 699A single nucleotide polymorphisms. Prostatic cancer overexpresses 0ATP1B3 compared with normal or benign hyperplastic tissue; patients with SLC01B3 334GG/699AA haplotype showed longer median survival (8.5 versus 6.4 years; P = 0.020) and improved survival probability at 10 years (42% versus 23%; P < 0.023) than patients carrying TT/AA and TG/GA haplotypes. Conclusions: The common SLC01B3 GG/AA haplotype is associated with impaired testosterone transport and improved survival in patients with prostatic cancer.

Original languageEnglish (US)
Pages (from-to)3312-3318
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number11
DOIs
StatePublished - Jun 1 2008

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Haplotypes
Androgens
Testosterone
Prostatic Neoplasms
Survival
Castration-Resistant Prostatic Neoplasms
Genotype
Organic Anion Transporters
Prostatic Hyperplasia
Fluorescence Microscopy
Single Nucleotide Polymorphism
Prostate
Neoplasms
Research Design
Steroids
Hormones
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Effect of SLC01B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-Lndependent prostatic cancer. / Hamada, Akinobu; Sissung, Tristan; Price, Douglas K.; Danesi, Romano; Chau, Cindy H.; Sharifi, Nima; Venzon, David; Maeda, Kenji; Nagao, Keisuke; Sparreboom, Alex; Mitsuya, Hiroaki; Dahut, William L.; Figg, William D.

In: Clinical Cancer Research, Vol. 14, No. 11, 01.06.2008, p. 3312-3318.

Research output: Contribution to journalArticle

Hamada, A, Sissung, T, Price, DK, Danesi, R, Chau, CH, Sharifi, N, Venzon, D, Maeda, K, Nagao, K, Sparreboom, A, Mitsuya, H, Dahut, WL & Figg, WD 2008, 'Effect of SLC01B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-Lndependent prostatic cancer', Clinical Cancer Research, vol. 14, no. 11, pp. 3312-3318. https://doi.org/10.1158/1078-0432.CCR-07-4118
Hamada, Akinobu ; Sissung, Tristan ; Price, Douglas K. ; Danesi, Romano ; Chau, Cindy H. ; Sharifi, Nima ; Venzon, David ; Maeda, Kenji ; Nagao, Keisuke ; Sparreboom, Alex ; Mitsuya, Hiroaki ; Dahut, William L. ; Figg, William D. / Effect of SLC01B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-Lndependent prostatic cancer. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 11. pp. 3312-3318.
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abstract = "Purpose: The organic anion transporter 0ATP1B3, encoded by SLC01B3, is involved in the transport of steroid hormones. However, its role in testosterone uptake and clinical outcome of prostatic cancer is unknown. This study examined (a) the SLC01B3 genotype in cancer cells as well as the uptake of testosterone by cells transfected with genetic variants of SLC01B3; (b) the expression of 0ATP163 in normal prostate, benign prostatic hyperplasia, and prostatic cancer; and (c) the role of SLC01B3 haplotype on clinical outcome of Caucasian patients with androgen-independent prostatic cancer. Experimental Design: SLC01B3 genotype was assessed in the NCI-60 panel of tumor cells by sequencing, whereas testosterone transport was analyzed in Cos-7 cells transfected with WT, 334G, and 699A SLC01B3 variants. 0ATP1B3 expression in prostatic tissues was examined by fluorescence microscopy, and the relationship between SLC01B3 haplotypes and survival was examined in patients. Results: Cells transfected with wild-type (334T/699G) SLC01B3, or with a vector containing either the 334G or 699A variants, actively transported testosterone, whereas its uptake was impaired in cells transfected with a gene carrying both 334G and 699A single nucleotide polymorphisms. Prostatic cancer overexpresses 0ATP1B3 compared with normal or benign hyperplastic tissue; patients with SLC01B3 334GG/699AA haplotype showed longer median survival (8.5 versus 6.4 years; P = 0.020) and improved survival probability at 10 years (42{\%} versus 23{\%}; P < 0.023) than patients carrying TT/AA and TG/GA haplotypes. Conclusions: The common SLC01B3 GG/AA haplotype is associated with impaired testosterone transport and improved survival in patients with prostatic cancer.",
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T1 - Effect of SLC01B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-Lndependent prostatic cancer

AU - Hamada, Akinobu

AU - Sissung, Tristan

AU - Price, Douglas K.

AU - Danesi, Romano

AU - Chau, Cindy H.

AU - Sharifi, Nima

AU - Venzon, David

AU - Maeda, Kenji

AU - Nagao, Keisuke

AU - Sparreboom, Alex

AU - Mitsuya, Hiroaki

AU - Dahut, William L.

AU - Figg, William D.

PY - 2008/6/1

Y1 - 2008/6/1

N2 - Purpose: The organic anion transporter 0ATP1B3, encoded by SLC01B3, is involved in the transport of steroid hormones. However, its role in testosterone uptake and clinical outcome of prostatic cancer is unknown. This study examined (a) the SLC01B3 genotype in cancer cells as well as the uptake of testosterone by cells transfected with genetic variants of SLC01B3; (b) the expression of 0ATP163 in normal prostate, benign prostatic hyperplasia, and prostatic cancer; and (c) the role of SLC01B3 haplotype on clinical outcome of Caucasian patients with androgen-independent prostatic cancer. Experimental Design: SLC01B3 genotype was assessed in the NCI-60 panel of tumor cells by sequencing, whereas testosterone transport was analyzed in Cos-7 cells transfected with WT, 334G, and 699A SLC01B3 variants. 0ATP1B3 expression in prostatic tissues was examined by fluorescence microscopy, and the relationship between SLC01B3 haplotypes and survival was examined in patients. Results: Cells transfected with wild-type (334T/699G) SLC01B3, or with a vector containing either the 334G or 699A variants, actively transported testosterone, whereas its uptake was impaired in cells transfected with a gene carrying both 334G and 699A single nucleotide polymorphisms. Prostatic cancer overexpresses 0ATP1B3 compared with normal or benign hyperplastic tissue; patients with SLC01B3 334GG/699AA haplotype showed longer median survival (8.5 versus 6.4 years; P = 0.020) and improved survival probability at 10 years (42% versus 23%; P < 0.023) than patients carrying TT/AA and TG/GA haplotypes. Conclusions: The common SLC01B3 GG/AA haplotype is associated with impaired testosterone transport and improved survival in patients with prostatic cancer.

AB - Purpose: The organic anion transporter 0ATP1B3, encoded by SLC01B3, is involved in the transport of steroid hormones. However, its role in testosterone uptake and clinical outcome of prostatic cancer is unknown. This study examined (a) the SLC01B3 genotype in cancer cells as well as the uptake of testosterone by cells transfected with genetic variants of SLC01B3; (b) the expression of 0ATP163 in normal prostate, benign prostatic hyperplasia, and prostatic cancer; and (c) the role of SLC01B3 haplotype on clinical outcome of Caucasian patients with androgen-independent prostatic cancer. Experimental Design: SLC01B3 genotype was assessed in the NCI-60 panel of tumor cells by sequencing, whereas testosterone transport was analyzed in Cos-7 cells transfected with WT, 334G, and 699A SLC01B3 variants. 0ATP1B3 expression in prostatic tissues was examined by fluorescence microscopy, and the relationship between SLC01B3 haplotypes and survival was examined in patients. Results: Cells transfected with wild-type (334T/699G) SLC01B3, or with a vector containing either the 334G or 699A variants, actively transported testosterone, whereas its uptake was impaired in cells transfected with a gene carrying both 334G and 699A single nucleotide polymorphisms. Prostatic cancer overexpresses 0ATP1B3 compared with normal or benign hyperplastic tissue; patients with SLC01B3 334GG/699AA haplotype showed longer median survival (8.5 versus 6.4 years; P = 0.020) and improved survival probability at 10 years (42% versus 23%; P < 0.023) than patients carrying TT/AA and TG/GA haplotypes. Conclusions: The common SLC01B3 GG/AA haplotype is associated with impaired testosterone transport and improved survival in patients with prostatic cancer.

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