Influences Of HPV16E6/E7 Genes On The Human Keratinocyte's Biological Properties And Its Regulators

Human papillomaviruse (HPV) are small DNA viruses that infect epithelial cells and induce a wide variety of proliferative lesions in human. Up to now, more than 70 types of HPVs have been identified and each appears to display a preference for the anatomical site that it infects. Among these types, 35 are related to the infection of the genital epithelium and considered to be sexually transmitted. Though the infection caused by the majority of HPVs results in chronic benign proliferative lesions. Several types of HPVs are found responsible for anogenital cancer. Among these, HPV16 is the most common type that is associated with cervical intraepithelial neoplasia and invasive squamous cell carcinoma. HPV16 has been shown to cause neoplastic transformation of NIH3T3, a mouse fibroblast line, in vitro. It can also immortalize human foreskin keratinocytes, but the immortalized cells do not form tumors in nude mice. Two HPV genes, E6 and E7, are important in the viral transfection process. E6 and E7 proteins, binding to and altering the tumor suppressor function of p53 and pRb, appear to play an important role in inducing cell immortalization. But E6 and E7 may target other critical cell growth regulatory genes. The mechanism of HPV E6 and E7 induced cell immortalization is not clear yet. Alterations in the expression of cell growth regulatory proteins in immortalization cells have been reported. However, there is few data on the alterations of cell growth regulation during the transition of normal cell to immortalization and/or malignant transformation, especially in the early stage of immortalization. HPV in vitro cell transfection provided an ideal model system for studying the molecular aspects of the interaction between viral and cellular genes, and the correlation between dysfunctional growth regulation and cell carcinogenesis.To analyze the role of E6/E7 genes in regulating cell growth and expression of cell growth regulating proteins and bcl-2, a series of experiments were conducted as follows:...