來自比利時(shí)的VIB  (the Flanders Institute for Biotechnology)的研究者發(fā)現(xiàn)一種新的抗癌基因,，據(jù)悉,，該基因首先在果蠅中被發(fā)現(xiàn),，研究者后來又在小鼠和人的基因組中找到同樣的基因。相關(guān)的成果以兩篇研究性文章形式公布在2月24日的PLoS  Biology上,。

VIB研究所的人類遺傳學(xué)研究中心的科學(xué)家發(fā)現(xiàn),，三個(gè)物種擁有同一種抑癌基因。關(guān)閉這一抑癌基因會(huì)導(dǎo)致癌癥發(fā)生,，而重新開啟這一基因有助抑制癌癥發(fā)生,。研究人員希望設(shè)計(jì)以這一基因?yàn)榘形坏乃幬镏委煱┌Y。

我們知道,，生命起源于一個(gè)細(xì)胞,，受精卵不斷分化，1變2,，2變4,，不斷延續(xù)。細(xì)胞分化的結(jié)果是形態(tài)功能各異的成體細(xì)胞出現(xiàn),，包括皮膚細(xì)胞,，肝細(xì)胞，神經(jīng)細(xì)胞等等,，這些高度分化的細(xì)胞都具有獨(dú)特的功能,，細(xì)胞們各自為政，各有不同,。

然而,，癌細(xì)胞卻不同，它超越了這一自然規(guī)律,，癌細(xì)胞沒有獨(dú)特的功能,，它始終像是呆在家（胚胎）中一樣，具有不受限制的復(fù)制能力,。研究者長(zhǎng)期以來都認(rèn)為,，在細(xì)胞分化的最后一步可能出現(xiàn)了一些錯(cuò)誤，導(dǎo)致分化成癌細(xì)胞,。

VIB的研究團(tuán)隊(duì)發(fā)現(xiàn),，有一個(gè)基因群控制細(xì)胞分化的最后步驟，這一步驟能確保細(xì)胞正確定型而不變?yōu)閻盒园┘?xì)胞,。VIB的科學(xué)家稱這一基因群為：Atonal  genes,，有趣的是，從果蠅到人類都存在有這一基因群,。

研究者發(fā)現(xiàn),，這種抑癌基因有一連串的基因，可謂是Atonal基因群,，其中同系物1  ATOH1基因與結(jié)腸癌有關(guān)聯(lián),，如果這一基因丟失將導(dǎo)致罹患結(jié)腸癌。原來,，ATOH1基因的主要功能是調(diào)節(jié)結(jié)腸上皮細(xì)胞分化的最后步驟,。研究者觀察了部分臨床病例，發(fā)現(xiàn)患有結(jié)腸癌的人類ATOH1基因失活,。

研究人員嘗試重新激活患者的ATOH1基因,，結(jié)果發(fā)現(xiàn)腫瘤細(xì)胞最終走向自我凋亡道路。

自從研究人員發(fā)現(xiàn)可以用化學(xué)藥物控制ATOH1基因后,，該基因就被看做是未來的癌癥治療的利器,。

筆者希望研究人員盡快找出與其他類型癌癥相關(guān)的Atonal基因,，比如說肝癌，胃癌的開關(guān),。 （生物谷Bioon.com）

生物谷推薦原始出處：

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.