Increased Expression of Androgen Receptor mRNA in Human Renal Cell Carcinoma Cells is Associated with Poor Prognosis in Patients with Localized Renal Cell Carcinoma

J Urol. 2015 Nov;194(5):1441-8. doi: 10.1016/j.juro.2015.03.078. Epub 2015 Mar 18.

Abstract

Purpose: The role of androgen receptor in renal cell carcinoma is not well understood. In this study the correlation between androgen receptor mRNA expression and clinicopathological features in patients with localized renal cell carcinoma was investigated. Additionally, human renal cell carcinoma cell lines were examined for the presence and effect of androgen receptor.

Materials and methods: Androgen receptor mRNA expression was evaluated by quantitative real-time polymerase chain reaction in 115 tumor samples from patients with primary pathological stage T1 or T2 (pT1/pT2) renal cell carcinoma and 57 specimens of corresponding normal kidney tissue. Reverse transcriptase-polymerase chain reaction and Western blot were done to examine the expression of androgen receptor in human renal cell carcinoma cell lines. Effects on cellular proliferation were investigated after activating and blocking androgen signaling in tissue culture.

Results: Androgen receptor mRNA expression levels were significantly higher in patients with pT2 tumors than in those with pT1 tumors (p = 0.011). Kaplan-Meier estimates revealed significant differences in time to progression and cancer specific survival between low and high androgen receptor mRNA expression groups regardless of gender. Multivariate Cox regression analysis demonstrated that the level of androgen receptor expression was an independent predictor of cancer specific survival (HR 15.546, 95% CI 1.320-183.131, p = 0.029). In tissue culture treatment with dihydrotestosterone caused proliferation in androgen receptor positive cell lines while enzalutamide resulted in reduced cell viability in a dose dependent manner.

Conclusions: In patients with localized renal cell carcinoma the androgen receptor mRNA expression level is associated with prognosis. In addition, cell culture data suggest that enzalutamide may have an effect in limiting the growth of androgen receptor positive renal cell carcinoma.

Keywords: MDV 3100; androgen; carcinoma; kidney; prognosis; receptors; renal cell.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Blotting, Western
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Neoplasm / genetics*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Androgen / biosynthesis
  • Receptors, Androgen / genetics*
  • Retrospective Studies
  • Time Factors
  • Young Adult

Substances

  • Biomarkers, Tumor
  • RNA, Neoplasm
  • Receptors, Androgen