【作者】 侯滨； 单吉贤；

【机构】 中国医科大学附属第一医院肿瘤外科；

【摘要】 大肠癌(colorectal carcinoma,CRC)是我国常见的恶性肿瘤之一,约有30％的患者仍在五年之内死于复发和远处转移。随着肿瘤分子水平研究的逐步深入,细胞内信号转导己成为普遍关注的生物学问题,它不仅调节多细胞生物的生长、发育、分裂及死亡等,并且与大肠癌等恶性肿瘤的发生发展密切相关。粘着斑激酶(focal adhesion kinase,FAK) 是一种胞内非受体型蛋白酪氨酸激酶(non-recepter protein tyrosine kinase,NRPTK),在整合素(integrin)介导的信号转导途径中起关键作用,与细胞的迁移、侵袭、存化等行为密切相关。整合素连接激酶(integrin-linked kinase, ILK)是最近发现的一种色(酪)氯酸蛋白激酶,是整合素激活MAPK／JNK以及引起细胞骨架改变的一条信号传导途径。 ILK的发现提示整合素对细胞的调节可能是通过或至少是部分通过ILK的作用实现的。肿瘤抑制基因PTEN(phosphatase and tensin homologue deleted on chromosome 10)又名 MMAC1基因,PTEN的蛋白磷酸酶活性是使粘着斑激酶 (Focal adhesion kinase,FAK)去磷酸化,FAK是整合蛋白介导的信号传导和细胞周期进展的关键分子,PTEN通过抑制FAK介导的细胞浸润、转移及其生长,从而抑制肿瘤的浸润转移。本实验采用免疫组织化学技术、RT-PCR方法及原位杂交方法检测大肠癌标本肿瘤组织、癌旁2cm、癌旁5cm 及远癌切端组织中FAK、ILK、PTEN mRNA的表达,研究其与大肠癌进展的相关性,试图为大肠癌的临床治疗及判断预后提供有价值的参考指标。更多还原

【Abstract】 Colorectal carcinoma, CRC is one of the most common malignant tumors in our country. Approximately 30% patients die of recurrence and distant metastasis within five years. With the gradual progression of tumor research on molecular level, intracellular signal transduction has already become the prevailingly attractive biological field, because not only does it regulate the growth, development, division and death of multicellular living things, but also is closely related to the growth and development of malignant tumors such as colorectal carcinoma. Focal adhesion kinase, FAK is a intracellular non-receptor protein tyrosine kinase, \RPTK, which is critical in the integrin-mediated signal transduction route and is closely related to cellular behavior such as migration, infiltration and metastasis. Integrin-linked kinase, ILK is recently discovered tryptofan(tyrosine) protein kinase, and is a signal transduction route of integrin activating MAPK/ JNK and inducing cellular skeleton alteration. The discovery of ILK suggests that integrin regulates cells perhaps through or at least partially through ILK’s factions. Tumor inhibitory gene PTEN (phosphatase and tensin ho-mologue deleted on chromosome 10), also called MMACI gene, whose protein phsophatase like activity enables dephosphalation of focal adhesion kinase, FAK, which in turn is a pivotal molecule in integrin-mediated signal transduction and cell cycle progression, inhibits the infiltration and metastasis of tumors through prohibiting the infiltration, metastasis and growth of cells mediated by FAK. This experiment use immunohistochemical technique, RT-PCR method and in situ hybridization to detect FAK, ILK, PTEN mRNA expression in tissue at the tumor site, 2 cm, 5 cm from the tumor and distal excised edge, then to indicate their relevancy to progression of colorectal carcinoma, and to make endeavor to offer some valuable referent criteria in clinical treatments and prognostic estimation of colorectal carcinoma.更多还原