Differential expression of cell adhesion genes: implications for drug resistance.
Differential expression of cell adhesion genes: implications for drug resistance.
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细胞粘附基因的差异表达：对耐药性的影响。
DOI：
10.1002/ijc.20671
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Bates,SusanE
中科院分区：
文献类型：
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作者：
Stein,WilfredD;Litman,Thomas;Fojo,Tito;Bates,SusanE
众所周知，来自组织如肾、胰腺、肝和胃的肿瘤特别难治疗。利用培养的细胞寻找新的抗癌药物已经产生了一些有效的治疗方法，但这些难治性肿瘤仍然很难治疗。将悬浮培养的细胞与作为聚集体彼此附着生长的类似细胞进行比较的研究表明，粘附于基底膜的细胞外基质赋予对细胞凋亡的抗性，从而赋予对细胞毒素的抗性。因此，表达与存活率差相关的基因可能通过这种基质对细胞凋亡的抑制起作用。事实上，基因表达和患者生存数据库的相关挖掘表明，转移性癌症患者的生存率低与一个共同主题的肿瘤表达高度相关：参与细胞粘附和细胞骨架的基因。如果参与将细胞束缚到细胞外基质的蛋白质在赋予耐药性方面很重要，那么通过设计针对这些蛋白质的药物来改善化疗是可能的。© 2004 Wiley利斯公司
It is well known that tumors arising from tissues such as kidney, pancreas, liver and stomach are particularly refractory to treatment. Searching for new anticancer drugs using cells in culture has yielded some effective therapies, but these refractory tumors remain intractable. Studies that compare cells grown in suspension to similar cells grown attached to one another as aggregates have suggested that it is adhesion to the extracellular matrix of the basal membrane that confers resistance to apoptosis and, hence, resistance to cytotoxins. The genes whose expression correlates with poor survival might, therefore, act through such a matrix‐to‐cell suppression of apoptosis. Indeed, correlative mining of gene expression and patient survival databases suggests that poor survival in patients with metastatic cancer correlates highly with tumor expression of a common theme: the genes involved in cell adhesion and the cytoskeleton. If the proteins involved in tethering cells to the extracellular matrix are important in conferring drug resistance, it may be possible to improve chemotherapy by designing drugs that target these proteins. © 2004 Wiley‐Liss, Inc.