MODULATION OF THE TUMORIGENICITY OF TRANSFORMED CELLS

实验性人尖锐湿疣可由人乳头瘤病毒引起

Experimental human condylomata can be generated by human papillomavirus type 11 (HPV-11) infection in vitro of human foreskin or human cervix tissue chips and subsequent in vivo transplantation to the renal capsule of athymic mice. Three months after infection, infected xenogafts are classified as mild to moderate dysplasias and resemble, in every measurable way, lesions seen in patients. These experimental condylomata express a full repertoire of HPV-11 genes and make recoverable amounts of infectious HPV-11. Transformed grafts are assumed to have alterations in expression of their cellular transcripts that affect cell phenotype. To date, it has not been possible to productively infect human tissue grafts with HPV-16. HPV-16 DNA, however, can be introduced into human cervix or foreskin keratinocytes, and cells exhibiting extended life span in culture have been derived. Transfection of ras oncogene DNA during or after HPV-16 DNA transfection results in cells that are tumorigenic in nude mice. Transformation of other cell types has also been accomplished. HPV-16 DNA or HPV-16 DNA plus ras DNA transformed cell lines retain copies of the input DNA and mainly express HPV-16 genes. The transformed cells derived in this laboratory and those derived by others are assumed to also have alterations in cellular transcript expressions that affect cell phenotype. Such alterations may differ in whole, or in part, from the ones found in HPV-11 infected cells. The goal of this research program is to identify and characterize the biological significance of such changes.