“胃腸道間質(zhì)瘤” (GISTs)發(fā)生在“Cajal間質(zhì)細胞”中，它們是嵌入在胃腸道肌肉組織中的細胞,，在那里它們產(chǎn)生電節(jié)律。現(xiàn)在Chi等人發(fā)現(xiàn),，轉(zhuǎn)錄因子ETV1是這些細胞的發(fā)育所必需的，而且該因子還促進腫瘤發(fā)育,。KIT基因（經(jīng)常被GIST中的突變激發(fā)）在“Cajal間質(zhì)細胞”的轉(zhuǎn)化中與ETV1配合（部分是通過促進ETV1的穩(wěn)定性來進行這種配合的）。ETV1似乎在所有GISTs中都以高水平存在,，使其成為用于醫(yī)學(xué)診斷的生物標(biāo)記的一個候選對象,，而ETV1阻斷藥物也可能會被證明對于抗藥性GIST有療效,。（生物谷 Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature09409
ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours
Ping Chi,Yu Chen,Lei Zhang,Xingyi Guo,John Wongvipat,Tambudzai Shamu,Jonathan A. Fletcher,Scott Dewell,Robert G. Maki,Deyou Zheng,Cristina R. Antonescu,C. David Allis& Charles L. Sawyers
Gastrointestinal stromal tumour (GIST) is the most common human sarcoma and is primarily defined by activating mutations in the KIT or PDGFRA receptor tyrosine kinases1, 2. KIT is highly expressed in interstitial cells of Cajal (ICCs)—the presumed cell of origin for GIST—as well as in haematopoietic stem cells, melanocytes, mast cells and germ cells2, 3. Yet, families harbouring germline activating KIT mutations and mice with knock-in Kit mutations almost exclusively develop ICC hyperplasia and GIST4, 5, 6, 7, suggesting that the cellular context is important for KIT to mediate oncogenesis. Here we show that the ETS family member ETV1 is highly expressed in the subtypes of ICCs sensitive to oncogenic KIT mediated transformation8, and is required for their development. In addition, ETV1 is universally highly expressed in GISTs and is required for growth of imatinib-sensitive and resistant GIST cell lines. Transcriptome profiling and global analyses of ETV1-binding sites suggest that ETV1 is a master regulator of an ICC-GIST-specific transcription network mainly through enhancer binding. The ETV1 transcriptional program is further regulated by activated KIT, which prolongs ETV1 protein stability and cooperates with ETV1 to promote tumorigenesis. We propose that GIST arises from ICCs with high levels of endogenous ETV1 expression that, when coupled with an activating KIT mutation, drives an oncogenic ETS transcriptional program. This differs from other ETS-dependent tumours such as prostate cancer, melanoma and Ewing sarcoma where genomic translocation or amplification drives aberrant ETS expression9, 10, 11. It also represents a novel mechanism of oncogenic transcription factor activation.
