Roles of Sex and Non-Sex Hormones in Liver Carcinogenesis in the Zebrafish Model
Zhiyuan Gong*, Chuan Yan, Qiqi Yang, Yan Li and Hankun Li
Department of Biological Sciences, National University of Singapore, Singapore
In the past few years, we have generated several liver cancer models by inducible expression of a selected driver oncogene in transgenic zebrafish. These zebrafish liver cancer models showed apparent sex disparity with males developing faster and more severe liver cancer, similar to human liver cancer patients. We found that female hormone (17β-estradiol) could generally alleviate liver tumors while male hormone (11-ketotesterone) accelerated liver cancer. By liver-specific knockout of the androgen receptor gene, we observed significant attenuation of liver carcinogenesis in male fish, further confirming the role of androgen in liver carcinogenesis. Interestingly we also found two non-sex hormones, cortisol and serotonin, played important roles in male dominant liver cancer. Cortisol, an adrenal hormone involving in stress, was greatly elevated in male liver tumors. Inhibition of cortisol signaling significantly mitigated hepatocarcinogenesis through reduction of inflammatory cells. Similarly, serotonin, a neurotransmitter, was also highly elevated in male liver tumors and it could activate hepatic stellate cells which in turn further stimulated hepatocarcinogenesis. Thus, our works demonstrated that both sex and non-sex hormones are involved in sex disparity of liver cancer. The correlation of cortisol or serotonin to liver cancer was also found in liver disease samples of human patients.
Acknowledgement: Supported by Ministry of Education, Singapore
Key Words: liver cancer, sex hormone, androgen, estrogen, androgen receptor, cortisol, serotonin, zebrafish
Zhiyuan Gong*, Chuan Yan, Qiqi Yang, Yan Li and Hankun Li
Department of Biological Sciences, National University of Singapore, Singapore
In the past few years, we have generated several liver cancer models by inducible expression of a selected driver oncogene in transgenic zebrafish. These zebrafish liver cancer models showed apparent sex disparity with males developing faster and more severe liver cancer, similar to human liver cancer patients. We found that female hormone (17β-estradiol) could generally alleviate liver tumors while male hormone (11-ketotesterone) accelerated liver cancer. By liver-specific knockout of the androgen receptor gene, we observed significant attenuation of liver carcinogenesis in male fish, further confirming the role of androgen in liver carcinogenesis. Interestingly we also found two non-sex hormones, cortisol and serotonin, played important roles in male dominant liver cancer. Cortisol, an adrenal hormone involving in stress, was greatly elevated in male liver tumors. Inhibition of cortisol signaling significantly mitigated hepatocarcinogenesis through reduction of inflammatory cells. Similarly, serotonin, a neurotransmitter, was also highly elevated in male liver tumors and it could activate hepatic stellate cells which in turn further stimulated hepatocarcinogenesis. Thus, our works demonstrated that both sex and non-sex hormones are involved in sex disparity of liver cancer. The correlation of cortisol or serotonin to liver cancer was also found in liver disease samples of human patients.
Acknowledgement: Supported by Ministry of Education, Singapore
Key Words: liver cancer, sex hormone, androgen, estrogen, androgen receptor, cortisol, serotonin, zebrafish