来自比利时的VIB (the Flanders Institute for Biotechnology)的研究者发现一种新的抗癌基因，据悉，该基因首先在果蝇中被发现，研究者后来又在小鼠和人的基因组中找到同样的基因。相关的成果以两篇研究性文章形式公布在2月24日的PLoS Biology上。
VIB研究所的人类遗传学研究中心的科学家发现，三个物种拥有同一种抑癌基因。关闭这一抑癌基因会导致癌症发生，而重新开启这一基因有助抑制癌症发生。研究人员希望设计以这一基因为靶位的药物治疗癌症。
我们知道，生命起源于一个细胞，受精卵不断分化，1变2，2变4，不断延续。细胞分化的结果是形态功能各异的成体细胞出现，包括皮肤细胞，肝细胞，神经细胞等等，这些高度分化的细胞都具有独特的功能，细胞们各自为政，各有不同。
然而，癌细胞却不同，它超越了这一自然规律，癌细胞没有独特的功能，它始终像是呆在家（胚胎）中一样，具有不受限制的复制能力。研究者长期以来都认为，在细胞分化的最后一步可能出现了一些错误，导致分化成癌细胞。
VIB的研究团队发现，有一个基因群控制细胞分化的最后步骤，这一步骤能确保细胞正确定型而不变为恶性癌细胞。VIB的科学家称这一基因群为：Atonal genes，有趣的是，从果蝇到人类都存在有这一基因群。
研究者发现，这种抑癌基因有一连串的基因，可谓是Atonal基因群，其中同系物1 ATOH1基因与结肠癌有关联，如果这一基因丢失将导致罹患结肠癌。原来，ATOH1基因的主要功能是调节结肠上皮细胞分化的最后步骤。研究者观察了部分临床病例，发现患有结肠癌的人类ATOH1基因失活。
研究人员尝试重新激活患者的ATOH1基因，结果发现肿瘤细胞最终走向自我凋亡道路。
自从研究人员发现可以用化学药物控制ATOH1基因后，该基因就被看做是未来的癌症治疗的利器。
笔者希望研究人员尽快找出与其他类型癌症相关的Atonal基因，比如说肝癌，胃癌的开关。 （生物谷Bioon.com）
生物谷推荐原始出处：
PLoS Biol 7(2): e1000040 doi:10.1371/journal.pbio.1000040
The Atonal Proneural Transcription Factor Links Differentiation and Tumor Formation in Drosophila
Wouter Bossuyt1,2,3, Natalie De Geest1,2, Stein Aerts1,2, Iris Leenaerts1,2, Peter Marynen2,3,4, Bassem A. Hassan1,2,3*
1 Laboratory of Neurogenetics, Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium, 2 Department of Human Genetics, K.U. Leuven School of Medicine, Leuven, Belgium, 3 Doctoral Program in Molecular and Developmental Genetics, K.U. Leuven Group Biomedicine, Leuven, Belgium, 4 The Human Genome Laboratory, Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium
The acquisition of terminal cell fate and onset of differentiation are instructed by cell type–specific master control genes. Loss of differentiation is frequently observed during cancer progression, but the underlying causes and mechanisms remain poorly understood. We tested the hypothesis that master regulators of differentiation may be key regulators of tumor formation. Using loss- and gain-of-function analyses in Drosophila, we describe a critical anti-oncogenic function for the atonal transcription factor in the fly retina, where atonal instructs tissue differentiation. In the tumor context, atonal acts by regulating cell proliferation and death via the JNK stress response pathway. Combined with evidence that atonal's mammalian homolog, ATOH1, is a tumor suppressor gene, our data support a critical, evolutionarily conserved, function for ato in oncogenesis.
PLoS Biol 7(2): e1000039 doi:10.1371/journal.pbio.1000039
Atonal homolog 1 Is a Tumor Suppressor Gene
Wouter Bossuyt1,2,3, Avedis Kazanjian4, Natalie De Geest1,2, Sofie Van Kelst1,2, Gert De Hertogh5, Karel Geboes5, Greg P. Boivin6, Judith Luciani7, Francois Fuks7, Marinee Chuah8,9, Thierry VandenDriessche8,9, Peter Marynen2,3,10, Jan Cools2,3,10, Noah F. Shroyer4,11,12*, Bassem A. Hassan1,2,3*
1 Laboratory of Neurogenetics, Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium, 2 Department of Human Genetics, K.U. Leuven School of Medicine, Leuven, Belgium, 3 Doctoral Program in Molecular and Developmental Genetics, K.U. Leuven Group Biomedicine, Leuven, Belgium, 4 Division of Gastroenterology, Hepatology, & Nutrition, Children's Hospital Research Foundation, Cincinnati, Ohio, United States of America, 5 Department of Pathology, Leuven University Hospital, K.U. Leuven, Leuven, Belgium, 6 Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America, 7 Laboratory of Cancer Epigenetics, Faculty of Medicine, Free University of Brussels (U.L.B.), Brussels, Belgium, 8 The Vesalius Research Center, VIB, Leuven, Belgium, 9 The Vesalius Research Center, K.U. Leuven School of Medicine, Leuven, Belgium, 10 The Human Genome Laboratory, Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium, 11 Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio, United States of America, 12 Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, United States of America
Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation.
