Cervical cancer is one of the leading causes of death in women. Cervical cancer is preceded by an abnormal form of growth known as dysplasia or cervical intraepithelial neoplasia (CIN). Human papilloma virus (HPV) has been strongly implicated as an etiological agent in the development of cervical cancer. The products of two viral genes, E6 and E7, have been implicated in the development of cervical cancer, at least in part through their ability to bind to tumor suppressor genes. Their role in the development of cervical dysplasia is unknown. The long term goal of the project is to elucidate the cellular events necessary for the development of cervical malignancy.
The specific aim of this study is to elucidate the cellular target genes of HPV 16 E7. The approach involves the use of an inducible form of E7 to generate two populations of cells which differ only in the state of activation of E7. RNA from these populations will be compared by differential display to identify cellular transcripts induced or repressed by the action of E7. The nature of these transcripts will be characterized by sequencing and analysis of expression through the cell cycle. The role of E7 target genes in the development of dysplasia will be examined through the use of in situ hybridization on normal, dysplastic and malignant tissue specimens. In the long term, the investigator hopes that the identification of E7 target genes will generate a set of markers that will assist in the appropriate management of dysplastic lesions, and may provide clues for therapeutic intervention.
| Smith-McCune, K; Kalman, D; Robbins, C et al. (1999) Intranuclear localization of human papillomavirus 16 E7 during transformation and preferential binding of E7 to the Rb family member p130. Proc Natl Acad Sci U S A 96:6999-7004 |
