Frisch S M
La Jolla Cancer Research Foundation, CA 92037, USA.
Mutat Res. 1996 Feb 19;350(1):261-6. doi: 10.1016/0027-5107(95)00103-4.
Tumor suppressor genes such as Rb and p53 usually kill tumor cells when overexpressed ectopically. This is a consequence of their normal cell cycle regulatory functions. By contrast, the E1a gene of adenovirus, a common cold virus, converts tumor cells into viable normal cells. This has advantages for investigation and control of cancer. In particular, E1a is a master programmer of the epithelial phenotype. This provides a new tool for understanding the molecular basis of the epithelial-mesenchymal transition, and how it goes awry in cancer cells. Furthermore, epithelial cells are sensitive to a form of apoptosis - 'anoikis' - that is induced by detachment from extracellular matrix. This property confers strict anchorage-dependence. Transcriptional programming, by E1a or the formation of cell-cell junctional complexes, programs epithelial cells to be sensitive to anoikis.
诸如Rb和p53等肿瘤抑制基因在异位过表达时通常会杀死肿瘤细胞。这是它们正常细胞周期调节功能的结果。相比之下，腺病毒（一种常见的感冒病毒）的E1a基因可将肿瘤细胞转化为有活力的正常细胞。这对于癌症的研究和控制具有优势。特别是，E1a是上皮表型的主要编程因子。这为理解上皮-间质转化的分子基础以及它在癌细胞中如何出错提供了一种新工具。此外，上皮细胞对一种由与细胞外基质脱离诱导的凋亡形式——“失巢凋亡”敏感。这种特性赋予了严格的锚定依赖性。通过E1a进行转录编程或形成细胞-细胞连接复合物，可使上皮细胞对失巢凋亡敏感。
