The human papillomaviruses (HPV) are major etiologic agents of several human cancers and have been found in essentially all cervical cancers and a significant number of other anogenital cancers as well as oral, laryngeal, and nasal cancers. Cervical cancers are associated with a high risk subset of HPVs of which HPV-16 is the most common. The E6 and E7 viral oncogenes interfere with the functions of p53 and pRb, respectively, and thus disrupt regulation of the cell cycle and promote genomic instability. The E6 protein has also been shown to induce expression of telomerase. Only a subset of individuals with HPV infection will develop persistent infection, and only some of those individuals will develop low-grade lesions and an even smaller number will develop high-grade lesions and invasive cervical cancer. It is likely that additional environmental and genetic factors predispose individuals to progression. In addition, progression of high risk HPV infection to high grade lesions and invasive cervical cancer requires significantly long lag periods, consistent with the accumulation of additional genetic and/or epigenetic changes. These changes are manifested by alterations in cellular gene expression as well as key changes in the biological behavior of the cells. The goals of this project are to use microarray gene expression profiling and other methods of assessing gene expression to: 1) Identify biomarkers that predict which lesions will progress to cancer and which will remain benign or regress. 2) Identify pathways disrupted during cervical cancer progression. 3) Identify changes in cellular gene expression induced by HPV infection.
| Wang, Sophia S; Dasgupta, Abhijit; Sherman, Mark E et al. (2005) Towards improved biomarker studies of cervical neoplasia: effects of precolposcopic procedures on gene expression patterns. Diagn Mol Pathol 14:59-64 |
| Liu, Xuefeng; Yuan, Hang; Fu, Baojin et al. (2005) The E6AP ubiquitin ligase is required for transactivation of the hTERT promoter by the human papillomavirus E6 oncoprotein. J Biol Chem 280:10807-16 |
| Fu, Baojin; Quintero, Jesse; Baker, Carl C (2003) Keratinocyte growth conditions modulate telomerase expression, senescence, and immortalization by human papillomavirus type 16 E6 and E7 oncogenes. Cancer Res 63:7815-24 |
