Alterations of Fas (APO-1/CD 95) gene and its relationship with p53 in non small cell lung cancer
Alterations of Fas (APO-1/CD 95) gene and its relationship with p53 in non small cell lung cancer
复制标题
非小细胞肺癌Fas（APO-1/CD 95）基因的改变及其与p53的关系
作者：
L. Boldrini;P. Faviana;F. Pistolesi;S. Gisfredi;D. D. Quirico;M. Lucchi;A. Mussi;C. Angeletti;F. Baldinotti;A. Fogli;P. Simi;F. Basolo;G. Fontanini
Fas(APO-1/CD95)系统调节细胞死亡的一系列生理和病理过程。Fas的配体通过与跨膜细胞表面的Fas受体相互作用来诱导细胞凋亡。Fas系统的关键作用主要在免疫系统中被研究，但Fas突变是抵抗细胞凋亡信号的可能机制之一，也可能参与非淋巴系统恶性肿瘤的发病。为了更好地了解Fas系统在非小细胞肺癌(NSCLC)中的潜在作用，我们用聚合酶链式反应方法检测了102例肿瘤组织和44例正常肺组织中Fas和Fas配体的表达。虽然超过60%的被分析的人类非小细胞肺癌表达这两个基因，但它们似乎无法通过自分泌自杀在体内诱导细胞凋亡。在这方面，我们通过聚合酶链式反应、单链构象多态和DNA测序对79例患者的Fas基因启动子和整个编码区进行了检测。16例肿瘤(20.25%)在启动子和/或外显子区域有Fas改变。在所有病例中，样本均携带杂合性改变，且多数同时显示P53基因突变。此外，Fas mRNA表达的定量分析显示，高水平的Fas信使仅与P53野生型状态相关。综上所述，这些发现表明Fas/Fas-Ligand系统参与了NSCLC的发生发展，提示其凋亡功能的丧失可能与有助于癌细胞自我维持的P53改变有关。
The Fas (APO-1/CD95) system regulates a number of physiological and pathological processes of cell death. The ligand for Fas induces apoptosis by interacting with a transmembrane cell surface Fas receptor. The key role of the Fas system has been studied mostly in the immune system, but Fas mutations, one of the possible mechanisms for resistance to apoptosis signaling, may be involved in the pathogenesis of non-lymphoid malignancies as well. To better understand the potential involvement of Fas system in non-small cell lung cancer (NSCLC) we evaluated Fas and Fas-ligand mRNA expression by polymerase chain reaction in 102 tumor samples and in 44 normal surrounding tissues. Although over 60% of the human NSCLC analysed expressed both genes, they seem to be unable to induce apoptosis in vivo by autocrine suicide. In this regard, we investigated in 79 cases, the promoter and the entire coding region of the Fas gene by polymerase chain reaction, single strand conformation polymorphism and DNA sequencing for detecting putative alterations. Sixteen tumors (20.25 %) were found to have Fas alterations, in promoter and/or exon region. In all cases samples carried heterozygous alterations and mostly showed simultaneous mutations of p53 gene. Moreover, the quantitative analysis of Fas mRNA expression showed high levels of Fas messenger associated with p53 wild-type status alone. Taken together, these findings point to an involvement of Fas/Fas-ligand system in the development of NSCLC, suggesting that the loss of its apoptotic function might be linked to p53 alterations which contribute to the self-maintenance of cancer cells.
影响因子：
15.9
作者：
FIRESTEIN, GS;YEO, M;ZVAIFLER, NJ
通讯作者：
ZVAIFLER, NJ
人类非造血恶性肿瘤中可溶性 Fas (sFas) 水平升高。
影响因子：
11.2
作者：
Midis,GP;Shen,Y;Owen-Schaub,LB
通讯作者：
Owen-Schaub,LB