Background: The network interactions link human disease proteins to regulatory cellular pathways
leading to better understanding of protein functions and cellular processes. Revealing the network of signaling
pathways in cancer through protein-protein interactions at molecular level enhances our understanding of
Hepatocellular Carcinoma (HCC).
Objective: A rodent model for study of HCC was developed to identify differentially expressed proteins at very
early stage of cancer initiation and throughout its progression.
Methodology: HCC was induced by administrating N-Nitrosodiethylamine (DEN) and 2-aminoacetylfluorine
(2-AAF) to male Wistar rats. Proteomic approaches such as 2D-Electrophoresis, PD-Quest, MALDI-TOF-MS
and Western blot analyses have been used to identify, characterize and validate the differentially expressed
proteins in HCC-bearing animals vis-a-vis controls.
Results: The step-wise analysis of morphological and histological parameters revealed HCC induction and
tumorigenesis at 1 and 4 months after carcinogen treatment, respectively. We report a novel protein network of
735 different proteins out of which eight proteins are characterized by MALDI-TOF-MS analysis soon after
HCC was chemically induced in rats. We have analyzed four different novel routes representing the association
of experimentally identified proteins with HCC progression.
Conclusion: The study suggests that A-Raf, transthyretin and epidermal growth factor receptor play major role
in HCC progression by regulating MAPK signaling pathway and lipid metabolism leading to continuous proliferation,
neoplastic transformation and tumorigenesis.