Login to Access Video or Poster Abstract: MP60-08
Sources of Funding: Cancer Institute of New Jersey

Introduction

The presence of androgen receptor (AR) in renal cell carcinoma (RCC) has been shown to be associated with higher tumor stage irrespective of gender. Our previous data have also demonstrated that anti-androgen therapy results in tumor suppression in a xenograft model of AR-positive RCC. Therefore, we hypothesize that intratumoral steroidogenesis is a source of androgens in AR-positive RCC.

Methods

Using enzyme-linked immunosorbent assay (ELISA), testosterone (T) and dihydrotesterone (DHT) levels were measured in AR-positive human RCC cell lines and human female RCC tissues. Nude mice were also injected with an AR-positive RCC cell line, Caki2. When tumors became palpable, surgical castration was performed and anti-androgen therapies with enzalutamide and abiraterone acetate were initiated. ELISA was then used to measure serum and intratumoral androgen levels. Real-time polymerase chain reaction (RT-PCR) was used to measure the expression levels of key enzymes required for steroidogenesis in RCC cell lines, human RCC tissues, and xenografts.

Results

AR-positive human RCC cell lines and tissues were found to have elevated levels of androgens compared to AR-negative controls (p<0.05), and both expressed key enzymes required for intracellular steroidogenesis. Intratumoral androgen concentrations also remained high following castration even with significant reduction in the serum levels of androgen in a xenograft model. Significant reduction of intratumoral androgen levels was also seen with androgen synthesis inhibitor (p<0.05). Moreover, increased expressions of key enzymes were seen following castration in the xenografts.

Conclusions

Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC, and the androgen signaling axis is a potential target of intervention in AR-positive RCC.

Funding

Cancer Institute of New Jersey