Loss of tyrosine aminotransferase may involved in the pathogenesis of hepatocellular carcinoma

Abstract

Tyrosine aminotransferase gene (TAT) locates at chromosome arm 16q22.1, which is one of the most frequent deletion regions in hepatocellular carcinomas (HCC). Our previous study showed that none or low expression of TAT was observed both in HCC cases and cell lines. Over expression of TAT in HCC cell line QGY-7703 could inhibit tumorigenicity and cause spontaneous apoptosis. Later, a mouse model wasobtained by targeted disruption of the murine TAT in embryonic stem cells. Homozygous knockout mice (TAT -/-) lack TATmRNA and have a virtually complete TAT activity deficiency and significant higher tyrosine concentration. Feeding with high tyrosine food could induce the homozygous knockout mice develop corresponding phenotypes as Tyrosinaemia II- Richner-Hanhart syndrome in human patients. Also, 2 homozygous (TAT -/-) (3.50% n=57) and 1 heterozygous (TAT +/-) (1.25% n=80) spontaneously developed HCC within 1.5 years, while none wildtype developed tumor during the same time span. Thus, our results supposed that the loss of TAT may contribute to the pathogenesis of HCC.