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Prostate Cancer Prostatic Dis. 2019 Mar 19. doi: 10.1038/s41391-019-0141-6. [Epub ahead of print]

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

Author information

1
Virginia Mason Medical Center, Seattle, WA, USA.
2
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
3
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
4
Department of Pathology, University of Washington, Seattle, WA, USA.
5
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
6
Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, Bethesda, MD, USA.
7
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
8
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
9
Department of Medicine, University of Washington, Seattle, WA, USA.
10
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. emostagh@fredhutch.org.
11
Department of Medicine, University of Washington, Seattle, WA, USA. emostagh@fredhutch.org.
12
Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA. emostagh@fredhutch.org.

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 (pā€‰<ā€‰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.

PMID:
30890759
DOI:
10.1038/s41391-019-0141-6

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