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

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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.