Early upregulation of AR and steroidogenesis enzyme expression after 3 months of androgen-deprivation therapy

Agus Rizal A.H. Hamid, Harun W. Kusuma Putra, Ningrum Paramita Sari, Putri Diana, Saras Serani Sesari, Eka Novita, Fajar Lamhot Gultom, Meilania Saraswati, Budiana Tanurahardja, Asmarinah, Rainy Umbas, Chaidir A. Mochtar

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

BACKGROUND: Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, PCa recurrence and progression rates during ADT are high. Until now, there has been no evidence regarding when progression begins. This study evaluated the gene expression of intraprostatic androgen receptor (AR) and steroidogenic enzymes in the early stages of ADT. METHODS: Prostate tissue samples were taken from PCa patients with urinary retention who received ADT (ADT-PCa; n = 10) and were further subgrouped into ADT ≤12 months (n = 4) and ADT > 12 months (n = 6). The ADT-PCa tissues were then compared with BPH (n = 12) and primary (no treatment) PCa tissues (n = 16). mRNA for gene expression analysis of AR and steroidogenic enzymes was extracted from formalin-fixed paraffin embedded (FFPE) tissues and analyzed by real-time PCR. Protein expression was evaluated by immunohistochemistry with specific antibodies. RESULTS: AR gene expression was higher in the ADT-PCa group than in the BPH or primary PCa group. Both the ADT ≤12 and > 12 months subgroups had significantly higher relative gene expression levels of AR (p < 0.01 and 0.03, respectively) than the primary PCa group. In the ADT-PCa group, AR protein expression showed an increasing trend in the ADT ≤12 months subgroup and was significantly elevated in the ADT > 12 months subgroup compared with the PCa group (100%; p < 0.01). Half (50%) of the patients in the ADT ≤12 months subgroup were found to have upregulation of AR, and one showed upregulation beginning at 3 months of ADT. A trend toward elevated relative gene expression of SRD5A3 was also apparent in the ADT groups. CONCLUSION: AR and steroidogenic enzymes are upregulated in ADT-PCa patients as early as 3 months, without PSA elevation. Steroidogenic enzymes, particularly SRD5A3, were also upregulated before PSA rose.

Original languageEnglish
Number of pages1
JournalBMC Urology
Volume20
Issue number1
DOIs
Publication statusPublished - 19 Jun 2020

Keywords

  • AKR3C1 SRD5A1
  • Androgen receptor
  • SRD5A2
  • SRD5A3
  • Steroidogenic enzyme

Fingerprint

Dive into the research topics of 'Early upregulation of AR and steroidogenesis enzyme expression after 3 months of androgen-deprivation therapy'. Together they form a unique fingerprint.

Cite this