Abstract B58: Gene expression study on a highly aggressive canine transmissible venereal tumor of a NOD/SCID mice model

Abstract

Abstract We have set up a xenograft NOD/SCID mice model bearing canine transmissible venereal tumor (CTVT) (designated as MCTVT). In addition to the similarity of the tumor cells between CTVT and MCTVT, the insertion of the specific gene fragment in the 5′ end of c-myc characteristic for a CTVT cell was also confirmed in MCTVT. However, as inoculating back to dogs, the MCTVT showed a much more aggressive growth and much higher metastatic frequency than a common CTVT. The goal of this research was to explore the gene expression differences between CTVT and MCTVT, and tried to delineate the mechanisms of their growth pattern differences. The differential gene expressions between the 2 tumors were studied using Affymetrix. Studied by hierarchical analysis and filtering the differential expressed genes by 2-fold method, we have found 105 genes significantly up-regulated and 37 down-regulated in MCTVT comparing to CTVT. Many of these genes were previously published to be involved in the areas such as malignant candidate genes, important biological processes, tumor development and immune modulation. We then used Real-Time RT-PCR to study the top 30 up-regulated genes. Three genes (APOC1, MMP1 and KMO) were further confirmed that were significantly up-regulated in MCTVT. The three genes were then tested in 22 spontaneous canine mammary gland tumors (CMGT) using Real-Time RT-PCR, the results indicated that two out of the three up-regulated genes discriminated malignant from benign CMGT and their gene expression was significantly higher in grades 4 and 5 malignant CMGT than those from lower grade tumors. We are currently studying the activities of KMO in association with the tumor cell growth. This study presented the novel candidate gene (KMO) that might associate with the malignant growth of tumor cells and has potential to be used as a biological marker to differentiate degrees of malignancy. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B58.