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Determination of connexin gene contributing to suppression of canine mammary carcinogenesis and investigation of the mechanism

抑制犬乳腺癌发生的连接蛋白基因的测定及其机制研究

基本信息

批准号：
16580259
负责人：
YANO Tomohiro
金额：
$ 2.37万
依托单位：
National Institute of Health and Nutrition
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

The expression patterns of connexin (Cx) genes, a member of gap junctions, are tissue- and cell-specific, and the expressions are mostly down-regulated during carcinogenic processes, so the genes were adequate to monitor the development of the tumors. We examined the expression of Cx mRNAs in five canine normal mammary glands and mammary gland tumor samples by reverse transcriptase-coupled polymerase chain reaction (RT-PCR) and RT-realtime PCR. We observed the expression of Cx26 and Cx43 genes in all of the normal tissues by RT-PCR using specific primers from Cx26 and Cx43 genes. Also, we analyzed the expression patterns of Cx26 and Cx43 genes in several types of canine mammary gland tumors using the RT-PCR, and we observed that the down-regulation of Cx43 was associated with malignancy of canine mammary gland tumors. These RT-PCR results were confirmed by RT-realtime PCR. These results suggest that Cx43 plays an important role in progression of canine mammary gland tumors.In order to determine chemopreventive agents which have suppressive effects on cancer cells via the induction of Cx43 gene, we tried to pick up candidate agents, using a cancer cell culture system and a xenograft model. As a result, we determined a promising component from foods to induce the induction of Cx43 gene in cancer cells. Actually, the induction of Cx43 gene by the component played a critical role in causing effective tumor suppression of the xenograft model. Overall, it seems that agents inducing high expression of Cx43 gene acts as a preventive and therapeutic agent against canine mammary tumors.

缝隙连接蛋白（connexin，Cx）基因的表达具有组织和细胞特异性，且在肿瘤发生发展过程中表达下调，可用于肿瘤的监测。我们研究了Cx mRNA的表达在5个犬正常乳腺和乳腺肿瘤样品通过逆转录酶偶联聚合酶链反应（RT-PCR）和RT-realtime PCR。我们用Cx 26和Cx43基因的特异性引物，通过RT-PCR方法观察了Cx 26和Cx43基因在所有正常组织中的表达。同时，我们还利用RT-PCR技术分析了Cx 26和Cx43基因在几种类型犬乳腺肿瘤中的表达模式，发现Cx43基因的下调与犬乳腺肿瘤的恶性程度有关。这些RT-PCR结果通过RT-realtime PCR证实。本研究利用犬乳腺癌细胞培养系统和异种移植瘤模型，筛选出Cx43基因在犬乳腺癌发生发展过程中起重要作用的化学预防剂，以确定Cx43基因对癌细胞有抑制作用的化学预防剂。结果，我们确定了一种有希望的食物成分，以诱导癌细胞中Cx43基因的诱导。实际上，该组分对Cx43基因的诱导在引起异种移植模型的有效肿瘤抑制中起关键作用。总之，诱导Cx43基因高表达的药物似乎可作为犬乳腺肿瘤的预防和治疗药物。