意大利研究人員日前宣布,，他們發(fā)現(xiàn)一種基因變異與肺癌有關(guān)。
意大利米蘭大學(xué)等機(jī)構(gòu)的研究人員發(fā)現(xiàn),，一種名為NOTCH的基因變異與肺癌有關(guān),，原因在于負(fù)責(zé)控制這一基因的Numb蛋白質(zhì)對其喪失了控制力。研究表明,，33％肺癌患者體內(nèi)的NOTCH基因都發(fā)生了變異,。
研究人員下一步將開展臨床試驗(yàn)，研究對NOTCH基因進(jìn)行干預(yù)后的治療效果,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
