Published online: 3 August 2011 | doi:10.1038/nchina.2011.58
Medical genetics: A man's worst enemy
A protein kinase in the androgen-receptor signalling pathway promotes liver cancer in men
Original article citation
J. Clin. Invest. doi:10.1172/JCI45967 (2011).
© (2011) American Society for Clinical Investigation
Liver cancer is more prevalent in men than in women.
Recent studies have established the pivotal role of androgen receptor (AR) — the nuclear receptor that mediates the effects of testosterone in a wide range of physiological processes — in liver carcinogenesis, but the underlying molecular mechanisms remain unclear.
Alfred Sze Lok Cheng, Joseph Jao Yiu Sung and co-workers1 at the Chinese University of Hong Kong have now identified a protein kinase in the AR signalling pathway that drives liver carcinogenesis.
The researchers used genome-wide location analysis to identify genes that interact with AR, followed by genome-wide functional analysis to determine the function of these genes in normal liver and liver cancer cells.
They found that AR positively regulates the expression of the gene encoding cell cycle-related kinase (CCRK).
The researchers showed that in both liver cells and mice, CCRK overexpression induced cell cycle progression and promoted tumour formation (pictured), whereas CCRK knockdown caused cell cycle delay and decreased tumour growth.
This finding demonstrates that CCRK promotes liver carcinogenesis through the AR signalling pathway, and also explains why liver cancer is more prevalent in men than in women.
The authors of this work are from:
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China; Institute of Digestive Disease and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China; Department of Surgery, Chinese University of Hong Kong, Hong Kong, China; College of Life Sciences, Inner Mongolia University, Hohhot, China; Department of Chemistry, University of Hong Kong, Hong Kong, China; Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.
- Feng, H. et al. Cell cycle-related kinase is a direct androgen receptor-regulated gene that drives β-catenin/T cell factor-dependent hepatocarcinogenesis. J. Clin. Invest. doi:10.1172/JCI45967 (2011). | Article |