MODULATION OF THE TUMORIGENICITY OF TRANSFORMED CELLS

实验性人尖锐湿疣可由人乳头瘤病毒产生 人包皮或人宫颈的11型（HPV-11）体外感染 组织芯片和随后的肾包膜体内移植 无胸腺小鼠 感染后三个月，受感染的异种 分类为轻度至中度发育不良， 可测量的方式，在患者中看到的病变。 这些实验性湿疣 表达完整的HPV-11基因库，并产生可回收的 感染性HPV-11 转化的移植物被认为具有改变， 影响细胞表型的细胞转录物的表达。 迄今为止，还不可能有效地感染人体组织 HPV-16的移植物 然而，HPV-16 DNA可以被引入人类， 子宫颈或包皮角质形成细胞，以及寿命延长的细胞 在文化中是衍生出来的。 ras癌基因DNA转染的研究 HPV-16 DNA转染后， 裸鼠 其他细胞类型的转化也已被 完成了 HPV-16 DNA或HPV-16 DNA加ras DNA转化细胞 细胞系保留输入DNA的拷贝，主要表达HPV-16基因。 在本实验室中获得的转化细胞和由 其他人被认为也有细胞转录的改变， 影响细胞表型的表达。 这种改变可能会有所不同， 全部或部分来自HPV-11感染细胞中发现的那些。 这项研究计划的目标是确定和表征 这些变化的生物学意义。

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.