Mutational Analysis of Proapoptotic Integrin Beta 3 Cytoplasmic Domain in Common Human Cancers
Mutational Analysis of Proapoptotic Integrin Beta 3 Cytoplasmic Domain in Common Human Cancers
复制标题
人类常见癌症中促凋亡整合素 Beta 3 胞质结构域的突变分析
作者：
N. Yoo;Y. Soung;Sung;E. Jeong;S. Lee
越来越多的证据表明，细胞凋亡的失调参与了癌症的发展机制。整合素是介导细胞存活和迁移的细胞粘附受体。最近的一项研究表明，未连接的整合素β 3（ITGB 3）通过招募caspase-8诱导细胞凋亡。本研究的目的是探讨ITGB 3基因的遗传改变可能通过使ITGB 3的凋亡功能失活而参与人类癌症的发展的可能性。方法采用聚合酶链反应单链构象多态性技术，对100例胃癌、90例结直肠癌、100例非小细胞肺癌、43例膀胱癌和50例头颈部癌患者ITGB 3基因胞浆区编码区进行体细胞突变检测。结果我们在两个不相关的患者样本中发现了相同的ITGB 3突变（一个在结直肠癌中，另一个在膀胱癌中）。ITGB 3突变是一个错义突变，它将取代一个氨基酸（E757 K）。结论促凋亡基因ITGB 3胞浆区在人类常见肿瘤中很少发生突变，可能在肿瘤的发生发展中不起重要作用。
Aims Mounting evidence indicates that deregulation of apoptosis is involved in the mechanisms of cancer development. Integrins are cell adhesion receptors that mediate cell survival and migration. A recent study showed that unligated integrin beta 3 (ITGB3) induced apoptosis by recruitment of caspase-8. The aim of the present study was to explore the possibility that genetic alteration of the ITGB3 gene is involved in the development of human cancers possibly by inactivating the apoptosis function of ITGB3. Methods We analyzed the coding region of the cytoplasmic domain of the human ITGB3 gene for the detection of somatic mutations in 100 gastric, 90 colorectal, 100 non-small cell lung, 43 urinary bladder and 50 head-neck cancers by a polymerase chain reaction-based, single-strand conformation polymorphism. Results We found an identical ITGB3 mutation in two unrelated patient samples (one in colorectal and the other in bladder cancer). The ITGB3 mutation was a missense mutation which would substitute an amino acid (E757K). Conclusions The data suggested that the proapoptotic ITGB3 cytoplasmic domain is rarely mutated in common human cancers and may not play an important role in the development of the cancers.