Suppression of invasive characteristics by antisense introduction of overexpressed HOX genes in ovarian cancer cells.
Suppression of invasive characteristics by antisense introduction of overexpressed HOX genes in ovarian cancer cells.
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DOI：
10.3892/ijo.28.4.931
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发表时间：
2006-04
影响因子：
5.2
通讯作者：
T. Yamashita;Seishiro Tazawa;Zhao Yawei;H. Katayama;Yasuhito Kato;K. Nishiwaki;Y. Yokohama;M. Ishikawa
中科院分区：
文献类型：
--
作者：
T. Yamashita;Seishiro Tazawa;Zhao Yawei;H. Katayama;Yasuhito Kato;K. Nishiwaki;Y. Yokohama;M. Ishikawa
HOX基因编码转录因子，其功能是在胚胎发生过程中建立基本的身体模式并维持成人特定器官的功能。最近的研究表明 HOX 基因还参与一系列恶性肿瘤的肿瘤发生。为了阐明 HOX 基因是否与卵巢癌发生有关，我们使用来自手术样本的卵巢来源材料和来自五种不同细胞系的上皮性卵巢癌细胞创建了 HOX 基因的表达谱。实时定量 RT-PCR 检测表明，A 簇和 B 簇中有 14 个 HOX 基因过表达，但 C 簇和 D 簇中只有 2 个基因。在 16 个 HOX 基因中，在 A 簇和 B 簇中观察到 HOX3、HOX4 和 HOX7 旁系同源物的过表达，在所有旁系同源物中观察到 HOX13 的过表达。此外，HOXB7、HOXA13和HOXB13在癌细胞和组织中表现出高水平的过表达，而在正常对照中没有观察到或很少表达。为了检查过表达的 HOX 基因是否直接调节卵巢癌细胞的侵袭，我们通过电穿孔将过表达的 HOXB7 和 HOXB13 以及未表现出过表达的 HOXC5 的反义 DNA 片段引入 SKOV3 细胞中。反义引入后使用基质胶室进行化学侵袭测定表明，引入每个 HOXB7 和 HOXB13 反义的 SKOV3 细胞与亲本 SKOV3 细胞相比，侵袭能力分别降低 85% 和 50%。相反，导入反义HOXC5的细胞显示出侵袭能力没有显着差异。这些结果表明过度表达的 HOX 基因具有重要作用，特别是对于卵巢癌细胞的侵袭特征。
HOX genes encode transcription factors that function to establish basic body pattern during embryogenesis and maintain the function of specific organs in the adult. Recent studies have demonstrated that HOX genes are also involved in oncogenesis in a range of malignancies. To elucidate whether HOX genes contribute to ovarian carcinogenesis, we created an expression profile of HOX genes using ovarian derived materials from surgical samples and epithelial ovarian cancer cells derived from five different cell lines. Real-time quantitative RT-PCR assay indicated overexpression of 14 HOX genes in clusters A and B but only 2 genes in clusters C and D. Of the 16 HOX genes, overexpression of paralogs of HOX3, HOX4 and HOX7 is seen in cluster A and B, and of HOX13 in all paralogs. In addition, HOXB7, HOXA13 and HOXB13 showed high levels of overexpression in cancer cells and tissues whereas no or little expression was observed in normal controls. To examine whether overexpressed HOX genes regulate invasion of ovarian cancer cells directly, we introduced an antisense DNA fragment of overexpressed HOXB7 and HOXB13, and HOXC5 that did not show overexpression into SKOV3 cells by electroporation. Antisense introduction followed by chemoinvasion assay using matrigel chamber demonstrated that SKOV3 cells introduced an antisense of each HOXB7 and HOXB13 showed 85% and 50% reduction of invasion ability compared to the parental SKOV3 cells, respectively. In contrast, antisense of HOXC5 introduced cells showed no significant difference of the invasion ability. These results suggest an important role of overexpressed HOX genes, especially for invasive characteristics of ovarian cancer cells.