新的研究证实，通过导入一种叫做E47的蛋白可以诱导胰腺癌细胞回复为正常细胞。E47与特异的DNA序列结合，控制了与生长和分化相关的一些基因。
桑福德-伯纳姆医学研究所发育、衰老和再生项目客座教授Pamela Itkin-Ansari博士说：“第一次我们证实过表达一种基因可以降低胰腺癌细胞的促肿瘤潜力，将它们重编程为原始的细胞类型。
研究构建出了一种人类胰腺导管腺癌细胞系，其产生的E47比正常水平要高。E47增加使得细胞停滞在G0/G1生长期，退回去分化为一种腺泡细胞表型。体内研究表明，当将这些重编程癌细胞导入到小鼠体内时，相比于未处理的腺癌细胞它们形成肿瘤的能力显著下降。
加州大学圣地亚哥分校Moores癌症中心外科学教授、国家癌症研究所胰腺癌特别小组联合组长Andrew M. Lowy博士说：“当前都是采用细胞毒性药物来治疗胰腺癌，患者确诊后平均生存期仅为6个月，改善治疗是以天计算。发现我们可以让这些癌细胞后退分化为一种不具威胁性的表型令人感到鼓舞。
原文链接：The Basic Helix-Loop-Helix Transcription Factor E47 Reprograms human Pancreatic Cancer Cells to a Quiescent Acinar State With Reduced Tumorigenic Potential.
原文摘要：Objectives: Pancreatic ductal adenocarcinoma (PDA) initiates from quiescent acinar cells that attain a Kras mutation, lose signaling from basic helix-loop-helix (bHLH) transcriptionfactors, undergo acinar-ductal metaplasia, and rapidly acquire increased growth potential. We queried whether PDA cells can be reprogrammed to revert to their original quiescent acinar cell state by shifting key transcription programs.
Methods: Human PDA cell lines were engineered to express an inducible form of the bHLH protein E47. Gene expression, growth, and functional studies were investigated using microarray, quantitative polymerase chain reaction, immunoblots, immunohistochemistry, small interfering RNA, chromatin immunoprecipitation analyses, and cell transplantation into mice.
Results: In human PDA cells, E47 activity triggers stable G0/G1 arrest, which requires the cyclin-dependent kinase inhibitor p21 and the stress response protein TP53INP1. Concurrently, E47 induces high level expression of acinar digestive enzymes and feed forward activation of the acinar maturation network regulated by the bHLH factor MIST1. Moreover, induction of E47 in human PDA cells in vitro is sufficient to inhibit tumorigenesis.
Conclusions: Human PDA cells retain a high degree of plasticity, which can be exploited to induce a quiescent acinar cell state with reduced tumorigenic potential. Moreover, bHLH activity is a critical node coordinately regulating human PDA cell growth versus cell fate.
