Biological properties of the oncoproteins E6 and E7 from mucosal and cutaneous HPV types

Abstract

Through epidemiological and biochemical studies the role of mucosal HPV types in human cancer has been confirmed and the molecular mechanisms underlying the transformation process have been elucidated. However, although research on the cutaneous HPV types is progressing fast, many questions remain unanswered regarding their potential role in human skin carcinogenesis.This thesis describes the characterization of the biological properties of E6 and E7 proteins from mucosal and cutaneous HPV types using novel or previously described assays and models. First, we describe the development and use of an in vitro systems to evaluate and quantify the ability of the oncoprotein E7 to associate with pRb (chapter 2). However, we show that this binding although indicative of a high risk HPV type, does not necessarily correlate with in vivo carcinogenicity (chapter 3) and that other in vitro studies are essential to asses the carcinogenicity of any given HPV type. Next we focused on the cutaneous HPV type 38, which displays in vitro transforming properties and appears to be frequently present in NMSC. We show that this cutaneous HPV type can increase the risk for development of skin cancer (chapter 4)and we describe a novel HPV transformation mechanism (chapter 5).