意大利研究人员日前宣布，他们发现一种基因变异与肺癌有关。
意大利米兰大学等机构的研究人员发现，一种名为NOTCH的基因变异与肺癌有关，原因在于负责控制这一基因的Numb蛋白质对其丧失了控制力。研究表明，33％肺癌患者体内的NOTCH基因都发生了变异。
研究人员下一步将开展临床试验，研究对NOTCH基因进行干预后的治疗效果。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS December 10, 2009, doi: 10.1073/pnas.0907781106
Alterations of the Notch pathway in lung cancer
Britta Westhoffa,b,1, Ivan N. Colalucaa,b,1, Giovanni D'Arioa, Maddalena Donzellia,b, Daniela Tosonia,b, Sara Volorioa,b, Giuseppe Pelosib,c, Lorenzo Spaggiarib,c, Giovanni Mazzarola,b, Giuseppe Vialeb,c, Salvatore Pecea,b,c,2 and Pier Paolo Di Fiorea,b,c,2
aIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy;
bEuropean Institute of Oncology, Milan, Italy; and
CDipartimento di Medicina, Chirurgia ed Odontoiatria, Università degli Studi di Milano, Milan, Italy
Notch signaling regulates cell specification and homeostasis of stem cell compartments, and it is counteracted by the cell fate determinant Numb. Both Numb and Notch have been implicated in human tumors. Here, we show that Notch signaling is altered in approximately one third of non–small-cell lung carcinomas (NSCLCs), which are the leading cause of cancer-related deaths: in ≈30% of NSCLCs, loss of Numb expression leads to increased Notch activity, while in a smaller fraction of cases (around 10%), gain-of-function mutations of the NOTCH-1 gene are present. Activation of Notch correlates with poor clinical outcomes in NSCLC patients without TP53 mutations. Finally, primary epithelial cell cultures, derived from NSCLC harboring constitutive activation of the Notch pathway, are selectively killed by inhibitors of Notch (γ-secretase inhibitors), showing that the proliferative advantage of these tumors is dependent upon Notch signaling. Our results show that the deregulation of the Notch pathway is a relatively frequent event in NSCLCs and suggest that it might represent a possible target for molecular therapies in these tumors.
