INHIBITION OF HUMAN ONCOGENE EXPRESSION BY INTERFERON

延长的α/β干扰素(α/β干扰素)或重组 干扰素-β对长期转化的RS485、NIH 3T3细胞的作用 末端重复序列激活的Ha-ras原癌基因导致 在干扰素后很长一段时间内保持未转化表型的返回体 治疗已经停止。克隆的持久回复体 (Prs)产生大量ras编码的p21，并被 EJras DNA和转化对转化的折射 携带v-Ha-ras、v-ki-ras、v-abl或v-fes的逆转录病毒 致癌基因。在体外或体内进行短暂的治疗 胞苷类似物通过抑制DNA改变基因表达 甲基化导致PR的转化，而不是NIH 3T3的转化 细胞。我们希望研究这一持续性的机制 回归。 我们希望展示基因表达模式的改变 通过在cDNA文库细胞中鉴定持续回复体 在PR和RS485中差异表达的消息。这个 这些cDNA对RS485或RS485表型的影响 持续回复的细胞将通过将这些细胞 具有允许过度表达以下任一项的构造的细胞 消息或反义消息。差异大鼠的基因组克隆 还将获得表达基因和侧翼调控基因 所分析的地区。 我们也希望研究共转化的可能作用。 癌基因、内源性干扰素的产生和DNA甲基化 监管网站出现了持续回复的现象，并以 用不同的方法进一步研究PR对再转化的抗性 病毒和细胞癌基因。

Prolonged alpha/beta interferon (IFN-alpha/beta) or recombinant IFN-beta treatment of RS485, NIH 3T3 cells transformed by a long terminal repeat-activated Ha-ras proto-oncogene resulted in revertants that maintain a non-transformed phenotype long after IFN treatment had been discontinued. Cloned persistent revertants (PRs) produced large amounts of the ras-encoded p21 and were refractile to transformation by EJras DNA and by transforming retroviruses which carried the v-Ha-ras, v-Ki-ras, v-abl, or v-fes oncogene. Transient treatment either in vitro or in vivo with cytidine analogs that alter gene expression by inhibiting DNA methylation resulted in transformation of PR, but not of NIH 3T3 cells. We wish to study the mechanisms involved in this persistent reversion. We hope to demonstrate altered patterns of gene expression in the persistent revertants by identifying in cDNA libraries cell messages that are differentially expressed in PRs and RS485s. The potential of these cDNAs to affect the phenotype of RS485 or persistent revertant cells will be evaluated by transfecting these cells with constructs that will allow the over-expression of either message or anti-sense message. Genomic clones of differentially expressed gene will also be obtained and the flanking regulatory regions analyzed. We also wish to investigate the possible roles of co-transforming oncogenes, endogenous IFN production, and DNA methylation of regulatory sites in the phenomenon of persistent reversion, and to study further the resistance of PRs to re-transformation by various viral and cellular oncogenes.