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Association of prostate cancer SLCO gene expression with Gleason grade and alterations following androgen deprivation therapy

Prostate Cancer and Prostatic Diseases volume 22, pages 560–568 (2019)Cite this article

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Abstract

Background

SLCO-encoded transporters have been associated with progression to castration-resistant prostate cancer (CRPC) after initiation of androgen deprivation therapy (ADT). Although expressed at lower levels than in CRPC tissues, SLCO-encoded transporters may also play a role in response of primary prostate cancer (PCa) to ADT and biochemical recurrence.

Methods

We systematically explored expression of the 11 human SLCO genes in a large sample of untreated and ADT-treated normal prostate (NP) and primary PCa tissues, including tumors treated with neoadjuvant abiraterone.

Results

Transporters with the most recognized role in steroid uptake in PCa, including SLCO2B1 (DHEAS) and 1B3 (testosterone), were consistently detected in primary PCa. SLCO1B3 was nearly 5-fold higher in PCa vs NP with no difference in Gleason 3 vs 4 and no change with ADT. SLCO2B1 was detected at 3-fold lower levels in PCa than NP but was nearly 7-fold higher in Gleason 4 vs Gleason 3 and increased 3-fold following ADT (p < 0.05 for all).

Conclusions

We observed clear differences in SLCO expression in PCa vs NP samples, in Gleason 4 vs Gleason 3 tumors, and in ADT-treated vs untreated tissues. These findings are hypothesis generating due to small sample size, but suggest that baseline and ADT-induced changes in PCa OATP expression may influence steroid uptake and response to ADT, as well as uptake and response to drugs such as abiraterone and docetaxel which are also subject to OATP-mediated transport and are now being routinely combined with ADT in the metastatic castration sensitive setting.

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Acknowledgements

The authors wish to acknowledge technical assistance from Jennifer Noteboom and Lori Kollath who assisted with provision of clinical outcome data, as well as Drs. Daniel Lin, William Ellis, and Jonathan Wright for supporting collection of excess frozen prostate tissue at time of radical prostatectomy.

Funding

This work was supported by NIH grants (Pacific Northwest Prostate Cancer SPORE P50 CA097186 to LT, PSN, RBM, EAM; FHCRC Cancer Center Support Grant 5P30 CA015704-40 (PSN, EAM); DF/HCC SPORE P50 CA090381 to AGS, HY, MET, and SPB; P01 CA163227 to EAM, PSN, SPB); Prostate Cancer Foundation (Challenge Awards to EAM, PSN, MET, SPB; Young Investigator Awards to AGS, HE, EAM); Department of Defense Prostate Cancer Research Program (W81XWH-11-2-0154 to EAM; W81XWH-13-1-0267 and W81XWH-16-1-0433 to AGS; W81XWH-16-1-0431 to SPB and W81XWH-16-1-0432 to MET), the Intramural Research Program of the NIH, National Cancer Institute (AGS), and the Department of Veterans Affairs Puget Sound Health Care System (EAM).

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Author notes

  1. These authors contributed equally: Mazen Alsinnawi, Ailin Zhang

Authors and Affiliations

  1. Virginia Mason Medical Center, Seattle, WA, USA

    Mazen Alsinnawi, John Burns, April E. Slee & Christopher Porter

  2. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Ailin Zhang, Daniella Bianchi-Frias & Peter S. Nelson

  3. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Eunpi Cho & Elahe A. Mostaghel

  4. Department of Pathology, University of Washington, Seattle, WA, USA

    Xiaotun Zhang & Lawrence True

  5. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Adam Sowalsky & Steven Balk

  6. Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, Bethesda, MD, USA

    Adam Sowalsky

  7. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Huihui Ye

  8. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Mary-Ellen Taplin

  9. Department of Medicine, University of Washington, Seattle, WA, USA

    R. Bruce Montgomery & Elahe A. Mostaghel

  10. Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA

    Elahe A. Mostaghel

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Correspondence to Elahe A. Mostaghel.

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Alsinnawi, M., Zhang, A., Bianchi-Frias, D. et al. Association of prostate cancer SLCO gene expression with Gleason grade and alterations following androgen deprivation therapy. Prostate Cancer Prostatic Dis 22, 560–568 (2019). https://doi.org/10.1038/s41391-019-0141-6

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