Frisch S M
The Burnham Institute, La Jolla, California 92037, USA.
Adv Cancer Res. 2001;80:39-49. doi: 10.1016/s0065-230x(01)80011-7.
Adenovirus E1a proteins reverse-transform diverse human tumor cells in culture. This has stimulated interest in the arenas of clinical and basic cancer research. Clinically, cancer gene therapy trials on E1a are in progress, and drug discovery strategies based on E1a are being considered. Biologically, the effect of E1a is unique in that it overrides most or all oncogenic signaling pathways to yield nontumorigenic cells. Apparently, this is a consequence of the ability of E1a to reprogram transcription in tumor cells so as to produce an epithelial phenotype that is refractory to oncogenic growth stimulation. The molecular basis for this effect is emerging.
腺病毒E1a蛋白可在培养中使多种人类肿瘤细胞发生逆转转化。这激发了临床和基础癌症研究领域的兴趣。在临床上，针对E1a的癌症基因治疗试验正在进行中，基于E1a的药物研发策略也正在被考虑。在生物学方面，E1a的作用独特，因为它能超越大多数或所有致癌信号通路，从而产生非致瘤性细胞。显然，这是E1a能够对肿瘤细胞中的转录进行重新编程，进而产生对致癌生长刺激具有抗性的上皮表型的结果。这种作用的分子基础正在逐渐显现。
