**Part 2**

**Carcinogenesis / Invasion / Metastasis** 

100 Hepatocellular Carcinoma – Basic Research

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**5** 

 *U.S.A.* 

**Modulation of Cell Proliferation Pathways by** 

Jessica C. Casciano1\*, Sumedha Bagga1\*, Bei Yang1 and Michael J. Bouchard2

Globally, hepatocellular carcinoma (HCC) is the fifth most common cancer and the third highest cause of cancer-associated deaths. Although the development of HCC has been linked to exposure to various toxins or infectious agents, the majority of HCC cases are associated with chronic hepatitis B virus (HBV) infections [reviewed in (Block et al, 2003; Seeger et al, 2007)]. Worldwide, there are an estimated 350 million cases of chronic HBV infections, and approximately 25% of chronically HBV-infected individuals will eventually develop HCC [(Beasley et al, 1981); reviewed in (Seeger et al, 2007)]. The high global incidence of chronic HBV infections, high mortality rate of individuals with HCC, increased prevalence of HCC, and the close association between chronic HBV infections and HCC development have generated intense interest in understanding the molecular mechanisms that underlie the development of HBV-induced HCC. In this chapter, we provide a review of HBV biology and potential mechanisms that link a chronic HBV infection to the development of HCC. We specifically focus on activities of the HBV X protein (HBx), a multifunctional HBV protein that can alter hepatocyte physiology and stimulate HBV replication. While a brief survey of HBx activities that could influence HCC development is provided, we emphasize HBx regulation of intracellular calcium signaling and cell proliferation pathways as HBx activities that could

HBV is a member of the *Hepadnaviridae,* a family of hepatotropic viruses that predominately infect hepatocytes in their respective hosts; similar viruses have been isolated from apes, woodchucks, squirrels, ducks, geese, and cranes [reviewed in (Seeger et al, 2007)]. HBV has a highly compact DNA genome of about 3200 nucleotides in length that contains four overlapping open reading frames (ORFs); every nucleotide of the genome is in at least one

**1. Introduction** 

potentially influence hepatocyte transformation.

**2. Hepatitis B virus** 

 \*

Co-first authors

**the Hepatitis B Virus X Protein: A Potential** 

**Contributor to the Development of** 

**Hepatocellular Carcinoma** 

*1Graduate Program in Molecular and Cellular Biology 2Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia PA* 
