Tumor Virology (work group 7)

Control of cell proliferation, differentiation and apoptosis by the Human Papillomavirus E7 oncoprotein.

The group studies the regulation of cell proliferation, differentiation and apoptotic cell death by the HPV E7 oncoprotein. HPVs of the high-risk types have been recognized as main etiological factors for malignant diseases such as cervical cancer. These HPVs encode two viral oncoproteins, E6 and E7 and the permanent expression of these proteins is necesssary for the maintenance of the transforming phenotype. The function of these viral oncoproteins in the normal viral life cycle is to ensure viral replication in cells that have withdrawn from the cell cycle and are committed to differentiation, and the expression of the E7 oncoprotein has been shown to contribute to the uncoupling of cellular differentiation and proliferation in human keratinocytes. Other studies have been shown that both oncoproteins interfere with the control of apoptotic cell death. We presently focus on the investigation of the interaction of E7 with certain cellular target proteins in human epithelial cell culture models. Moreover, to better understand the role of E7 in vivo, we analyze the distribution of high risk E7 oncoproteins and their target proteins in malignant and premalignant cervical tumor biopsies. To do this, we developed highly specific anti high-risk-HPV E7 antibodies suitable for the E7-detection in cervical biopsies in situ. These anti-E7 antibodies may have diagnostic potential for the detection of the high-risk-E7 oncoproteins as tumour markers for cervical cancer.