Androgen receptors promote hepatitis B virus in growth and development of hepatoma cells

Dr. Ming-Heng Wu of the Institute of Basic Medical Sciences at National Cheng Kung University (NCKU), Taiwan, in collaboration with Prof. Chawnshang Chang's laboratory of University of Rochester (UR), United States, have discovered that androgen receptors (AR) can promote hepatitis B virus-induced hepatocarcinogenesis through modulation of hepatitis B virus (HBV) RNA transcription.

“Androgen Receptor Promotes Hepatitis B Virus-Induced Hepatocarcinogenesis Through Modulation of Hepatitis B Virus RNA Transcription”

The discovery has captured considerable attention of the field of hepatitis and liver research studies. It was published in the internationally renowned medical journal Science Translational Medicine on May 20th. The American Association for the Advancement of Science (AAAS) has announced this major discovery in a press conference held on May 20th in Washington, D.C., capital of the United States of America.

Dr. Ming-Heng Wu expressed, "According to the statistics of epidemiology, the chronic hepatitis B virus infection is an important factor in causing liver cancer. The higher the amount of hepatitis B virus in the serum, the higher the chance of getting liver cancer. Particularly, men are up to seven times more likely than women to develop liver cancer. Among hepatitis B virus carriers, men are also more likely to develop liver cancer than women. The evidences have suggested that serum androgen concentration androgen receptors may play a significant role in liver cancer induced by hepatitis B virus. However, there hasn't been any research done to validate the theory."

In view of this, advised by Associate Professor Yuh-Ling Chen of the NCKU Institute of Oral Medicine and the NCKU Institute of Basic Medical Sciences, then a PhD student, Dr. Ming-Heng Wu worked with Prof. Chawnshang Chang's laboratory at University of Rochester to engage in a research of androgen receptors and hepatitis B virus.

The research team used transgenic technology to create the first mouse in the world that was genetically modified to lack androgen receptor in its liver hepatocytes and infected with hepatitis B virus for subsequent animal experiments. In the animal experiment, it was proved that androgen receptors will increase the replication of hepatitis B virus and enhance the incidence of liver cancer. Since previous research studies have revealed that lowering the concentration of androgen in the serum could not effectively treat liver cancer, a new method to treat liver cancer by restraining androgen receptors in the liver cells has been discovered.

In the experiment, the team injected low doses of carcinogen, diethylnitrosamine (DEN), into normal mice and mice that were infected with hepatitis B virus, sixteen days after they were born. By week 22, only mice that were infected with hepatitis B virus had developed liver tumors.

The team further explored the role of androgen receptors in the process of hepatitis B virus causing liver tumors. They used normal mice and HBV transgenic mice lacking androgen receptors only in the liver hepatocytes. These mice were infected with hepatitis B virus and injected with diethylnitrosamine sixteen days after their birth. By week 22, mice that were infected with hepatitis B virus were six times more likely to develop liver tumors than mice infected with hepatitis B virus and lacking in androgen receptors in their liver hepatocytes. The evidences have shown that androgen receptors can promote hepatitis B virus in the growth and development of hepatoma cells. Furthermore, their results have demonstrated that targeting the androgen receptors, rather than the androgen, could be developed as a new therapy to battle HBV-induced hepatocellular carcinoma.

SOURCE National Cheng Kung University (NCKU), Taiwan