|Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
In order to understand how colorectal cancers convert into further invasive, expression profile of SW480 cells were compared to that of SW620 which was independently established with 1ymph node dissemination by SW480. About 5000 genes were analysis in each cells using a DNA microarray, selected 72 genes which were expressed over twice and 112 genes which were less than half in SW620, respectively. In a separate assessment by RT-PCR, expression of tissue inhibitors of matrix metalloproteinase were analyzed in each cells. Consistent with the previous reports, TIMP-1 was up- and TIMP-3 was down regulated in SW620. It has been demonstrated that SW620 behaves more invasive than SV480 in vitro or in vivo, further speculated that the gene silencing of TIMP-3 is involved in the phenotype. In our assay, however, both of cells shows low invasiveness similarly in vitro, or even in in vivo model for liver metastasis. To know the reason why both cells keep less-invasive, MT1-MMP, that is thought to be important for tumor invasion and one of the targets of TIMP-3, was evaluated on Western blot with an anti-MT1-MMP Antibody.
Actually the level of the expression was considerably low in both of |he tumor cells. On the other hand, SW620 showed, a rapid growing in vivo more than SW480. Next question would, then, be an address understanad how the proliferation could be related with the gene expression profile including TIMP-1 and -3.