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

Prostate Cancer Prostatic Dis. 2019 Dec;22(4):560-568. doi: 10.1038/s41391-019-0141-6. Epub 2019 Mar 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Androgen Antagonists / pharmacology*
  • Androgen Antagonists / therapeutic use
  • Androstenes / pharmacology
  • Androstenes / therapeutic use
  • Dehydroepiandrosterone Sulfate / metabolism
  • Disease Progression
  • Docetaxel / pharmacology
  • Docetaxel / therapeutic use
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Organic Anion Transporters / metabolism*
  • Prostate / pathology*
  • Prostate / surgery
  • Prostate-Specific Antigen / blood
  • Prostatectomy
  • Prostatic Neoplasms, Castration-Resistant / diagnosis
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Prostatic Neoplasms, Castration-Resistant / therapy*
  • Solute Carrier Organic Anion Transporter Family Member 1B3 / metabolism*
  • Testosterone / metabolism
  • Treatment Outcome


  • Androgen Antagonists
  • Androstenes
  • Organic Anion Transporters
  • SLCO1B3 protein, human
  • SLCO2B1 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Docetaxel
  • Testosterone
  • Dehydroepiandrosterone Sulfate
  • Prostate-Specific Antigen
  • abiraterone