Survivin-3B Gene Decreases the Invasion-Inhibitory Effect of Colon Cancer Cells With 5-Fluorouracil

Survivin-3B Gene Decreases the Invasion-Inhibitory Effect of Colon Cancer Cells With 5-Fluorouracil
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DOI:
10.3727/096504010x12767359113848
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发表时间:
2010-01-01
期刊:
影响因子:
3.1
通讯作者:
Yamaguchi, Akio
Yamaguchi, Akio
中科院分区:
医学2区
文献类型:
--
作者:
Sawai, Katsuji;Goi, Takanori;Yamaguchi, Akio

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生存素分子的表达已在多种类型的癌细胞中得到证实,包括结肠癌细胞,它们被认为是重要的抗凋亡分子。最近的研究揭示了生存素分子不同剪接形式的存在;然而,没有研究检查它们在胃肠道癌症中的表达。 2004年,我们报道了survivin-3B基因的存在,这是survivin的一种新型剪接变体。在这项研究中,我们研究了人类结肠癌与我们最近克隆的 survivin-3B 基因(编码区为 594 bp)之间的关系。在第一次检查中,通过 RT-PCR 分析了人结肠癌和邻近正常粘膜组织中的 survivin-3B 表达。还检查了其表达状态与临床病理参数和预后的关联。在 80 例原发性结肠癌中,有 37 例(46.3%)观察到 Survivin-3B mRNA 表达,但在邻近的正常结肠粘膜组织中未观察到。伴浆膜侵犯的结肠癌中survivin-3B基因表达率显着升高。 survivin-3B基因阳性原发性结肠癌患者的5年生存率为48.7%,明显低于survivin-3B基因阴性患者的5年生存率(75.4%)。在第二次检查中,将survivin-3B基因导入结肠癌细胞系DLD-1的细胞后,检查了5-氟尿嘧啶诱导的侵袭能力的变化。 5-氟尿嘧啶对survivin-3B基因转染的DLD-1细胞的侵袭抑制作用显着低于空载体基因转染的细胞。我们推测结肠癌中survivin-3B的表达是抗癌药物存在下癌细胞侵袭能力的重要因素。
The expression of survivin molecules has been confirmed in many types of cancer cells, including colon cancer cells, and they are considered important antiapoptotic molecules. Recent studies have revealed the existence of different splicing forms of survivin molecules; however, no studies have examined their expression in gastrointestinal cancers. In 2004, we reported the existence of the survivin-3B gene, a novel splice variant of survivin. In this study, we investigated the relationship between human colon cancer and our recently cloned survivin-3B gene with a coding region of 594 bp. In the first examination, survivin-3B expression was analyzed by RT-PCR in human colon cancer and adjacent normal mucosa] tissues. The associations of its expression status with clinicopathological parameters and the prognosis were also examined. Survivin-3B mRNA expression was observed in 37 (46.3%) of 80 primary colon cancers, but not in the adjacent normal colonic mucosal tissue. The rate of survivin-3B gene expression was significantly higher in colon cancer with serosal invasion. The 5-year survival rate of patients with survivin-3B gene-positive primary colon cancer was significantly poorer, at 48.7%, than that (75.4%) of survivin-3B gene-negative patients. In the second examination, after the introduction of the survivin-3B gene into cells of the colon cancer cell line DLD-1, 5-fluorouracil-induced changes in their invasive capacity was examined. The invasion-inhibitory effect of 5-fluorouracil on survivin-3B gene-transfected DLD-1 cells was significantly lower than their empty vector gene-transfected counterparts. We speculate that survivin-3B expression in colon cancer is an important factor involved in the invasive capacity of cancer cells in the presence of anticancer drug.