Angiogenin mediates androgen-stimulated growth of prostate cancer cells and correlates with castration resistance

• Published in: Molecular cancer research Vol. 11; no. 10; pp. 1203 - 1214
• Main Authors: Li, Shuping, Hu, Miaofen G., Sun, Yeqing, Yoshioka, Norie, Ibaragi, Soichiro, Sheng, Jinghao, Sun, Guangjie, Kishimoto, Koji, Hu, Guo-fu
• Format: Journal Article
• Language: English
• Published: 12.07.2013
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1541-7786.MCR-13-0072

Androgen receptor (AR) is a critical effector of prostate cancer (PCa) development and progression. Androgen-dependent PCa rely on the function of AR for growth and progression. Many castration-resistant PCa continue to depend on AR signaling for survival and growth. Ribosomal RNA (rRNA) is essential for both androgen-dependent and castration-resistant growth of PCa cells. During androgen-dependent growth of prostate cells, androgen-AR signaling leads to the accumulation of rRNA. However, the mechanism by which AR regulates rRNA transcription is unknown. We have found that angiogenin (ANG), the 5 th member of the vertebrate-specific, secreted ribonuclease superfamily that is upregulated in PCa, mediates androgen-stimulated rRNA transcription in PCa cells. Upon androgen stimulation, ANG undergoes nuclear translocation in androgen-dependent PCa cells where it binds to the ribosomal DNA (rDNA) promoter and stimulates rRNA transcription. ANG antagonists inhibit androgen-induced rRNA transcription and cell proliferation in androgen-dependent PCa cells. ANG also mediates androgen-independent rRNA transcription. It undergoes constitutive nuclear translocation in androgen-insensitive PCa cells, resulting in a constant rRNA overproduction thereby stimulating cell proliferation. ANG overexpression in androgen-dependent PCa cells enables castration-resistant growth of otherwise androgen-dependent cells. Thus, ANG-stimulated rRNA transcription is not only an essential component for androgen-dependent growth of PCa, but also contributes to the transition of PCa from androgen-dependent to castration-resistant growth status.