Induction of KIFC1 expression in gastric cancer spheroids
Induction of KIFC1 expression in gastric cancer spheroids
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DOI：
10.3892/or.2016.4781
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发表时间：
2016-07-01
期刊：
影响因子：
4.2
通讯作者：
Yasui, Wataru
中科院分区：
文献类型：
--
作者：
Oue, Naohide;Mukai, Shoichiro;Yasui, Wataru
胃癌是人类最常见的癌症之一。球状集落形成是表征肿瘤干细胞的一种有效模型。然而，从GC细胞获得的球状集落的基因表达谱尚未被检测。我们用人类基因组U133 Plus 2.0芯片对MKN-45和MKN-74 GC细胞系的球体形成细胞和亲本细胞进行了基因芯片分析。在两个GC系中，KIFC1家族成员在球体形成细胞中的表达是亲本细胞的2倍。与阴性对照相比，KIFC1siRNA转染组MKN-45细胞的球体数量和大小均显著减少。对114例胃癌组织进行免疫组织化学分析，42例(37%)胃癌组织中KIFC1表达阳性。KIFC1阳性的GC病例在III/IV期患者中的发生率高于I/II期患者。肠型胃癌KIFC1阳性例数明显高于弥漫型胃癌。此外，KIFC1阳性的GC具有较高的Ki-67标记指数。Kaplan-Meier分析显示KIFC1的表达与生存无关。我们发现KIFC1在CD44阳性的GC细胞和ALDH1阳性的GC细胞中呈阳性表达。我们的结果表明KIFC1在GC中高表达。由于KIFC 1基因的敲除抑制了球体的形成，因此KIFC 1可能在肿瘤干细胞中发挥重要作用。
Gastric cancer (GC) is one of the most common human cancers. Spheroid colony formation is an effective model for characterization of cancer stem cells. However, gene expression profiles of spheroid colonies obtained from GC cells have not been examined. We performed microarray analyses by Human Genome U133 Plus 2.0 Array in spheroid body-forming and parental cells from MKN-45 and MKN-74 GC cell lines. Kinesin family member C1 (KIFC1) was expressed >2-fold higher in spheroid body-forming cells than in parental cells in both GC lines. Both the number and size of spheres from MKN-45 cells were significantly reduced upon KIFC1 siRNA-transfection compared with negative control siRNA-transfection. Immunohistochemical analysis of 114 GC tissue samples revealed that 42 (37%) of GC cases were positive for KIFC1 expression. GC cases positive for KIFC1 were found more frequently in stage III/IV cases than in stage I/II cases. GC cases positive for KIFC1 were found more frequently in intestinal type GC cases than in diffuse type GC cases. Furthermore, KIFC1-positive GC cases showed high Ki-67 labeling index. Kaplan-Meier analysis demonstrated that KIFC1 expression was not associated with survival. We found positive expression of KIFC1 in CD44-positive GC and aldehyde dehydrogenase 1 (ALDH1)-positive GC cells. Our results showed that KIFC1 is overexpressed in GC. Since knockdown of KIFC1 inhibited sphere formation, KIFC1 likely plays an important role in cancer stem cells.