2-D DIGE profiling of hepatocellular carcinoma tissues identified isoforms of far upstream binding protein (FUBP) as novel candidates in liver carcinogenesis.
Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide and is often characterized by aggressive tumour behaviour and poor prognosis. One of the major etiologies is hepatitis B or C virus (HBV or HCV) infections. In order to better comprehend the molecular mechanisms involved in HCC progression, we performed a systematic analysis on moderately and poorly differentiated human HCC tissues using 2-D DIGE coupled to MALDI-TOF/TOF MS. A total of 52 and 26 proteins were found to be dysregulated in moderately and poorly differentiated HCC tissues, respectively. For the first time, the over-expression of a novel protein family, far upstream binding proteins (FUBPs) was identified in both stages of HCC and confirmed by western blots. FUBPs are of particular interest due to their transcriptional activity on the oncogene, c-myc. It has generally been accepted that c-myc plays an important role in HCC progression but its exact activators remain poorly understood. Interestingly, we also observed elevated c-myc levels in the tissues used in this study by western blot analysis. We therefore propose that the FUBP family of proteins may be one of the possible upstream players that are involved in modulating the c-myc levels in HCC tumorigenesis.
Zubaidah
Ramdzan M
RM
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Tan
Gek San
GS
Tan
Sandra B E
SB
Lim
Seng Gee
SG
Lin
Qingsong
Q
Chung
Maxey C M
MC
D000595:Amino Acid Sequence; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C492258:FUBP1 protein, human; C105789:KHSRP protein, human; D020033:Protein Isoforms; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D004265:DNA Helicases