Author Description

This dissertation, "Overexpression of Translationally Controlled Tumor Protein (TCTP) Predisposes to Hepatocellular Carcinoma" by, Hon-man, Chan, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Hepatocellular carcinoma (HCC) is the most common tumors worldwide. In contrast to other cancers, the prognosis of HCC is extremely poor, with less that 5% of 5-year survival rate worldwide. From our previous studies, we isolated Chromodomain Helicases/ATPase DNA binding protein1-Like (CHD1L) gene from chromosome 1q21, and characterized it as a specific oncogene in HCC. By using 2D-PAGE and MALDI-TOF mass spectrometry approach, Translationally Controlled Tumor Protein (TCTP) was identified as a CHD1L target, which was preferentially expressed in CHD1L-transfected cells. TCTP is a highly conserved protein and expressed in almost all mammalian tissues. It has been reported that TCTP interacts with microtubules in a cell-cycle-dependent manner, and functions as a prosurvival factor and inhibiting apoptosis. To better understand the molecular mechanisms of HCC progression, the effect of TCTP overexpression in HCC and the mechanism by which TCTP regulated cell-cycle progression were elucidated in this study. CHD1L is a unique oncogene belongs to SNF2-like subfamily. Mechanistic studies found that CHD1L protein directly binds to the promoter region (nt -733 to -1,027) of TCTP and activated TCTP transcription. Investigation of clinical HCC specimens found that overexpression of TCTP was not only significantly associated with the advanced tumor stage (P = 0.037) and overall survival time of HCC patients (P = 0.034), bu