| Budget Amount *help |
¥3,750,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
The prognosis of patients with lung cancer is still poor due to its propensity for metastasis. Thus, it is highly dependent on the presence or absence of metastasis and on the effectiveness of treatment against it. However, molecular mechanisms of metastasis in lung cancer are still obscure. We established highly metastatic sublines, from the human lung adenocarcinoma cell lines, PC14, LCMS by in vivo selection. Compared to parental cells, these sublines developed significantly more metastatic nodules in the various organs, such as adrenal glands, bones, lymph nodes, lung after injection of 2 エ 106 cells into the tail vein of nude mice. There were no significant differences in the subcutaneous tumorigenicity in vivo and in the growth rates in vitro between high-metastatic sublines and parental cells. In addition, there were no significant differences in motility, invasiveness, and adherence between high-metastatic sublines and parental cells. A comparison of the expression of 36, 300 g
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enes by cDNA microarray revealed that 28 genes were differentially expressed between parental PC14 cells and high-metastatic PC14Ad cells. Among these, expression of four genes (HRB2, HS3ST3A1, RAB7, EDG-1) in the tissue specimen of human lung cancer and adjacent normal lung were analysed by quantitative real-time RT-PCR analysis. Expression of 3 genes was higher in the cancer tissue than in the normal lung. Expression of 1 genes was lower in the cancer tissue than in the normal lung. The differences in expression were significant in the two genes, suggesting that these two genes might be a key determinant of carcinogenesis and progression of human lung cancer. Expression of four genes in the tissue specimen was also compared between metastatic nodules and subcutaneous nodule of PC14Ad mouse models by quantitative real-time RT-PCR analysis. There were no differences between metastatic nodules and subcutaneous nodule in the high-metastatic PC14Ad cells, suggesting constitutive expression of these genes in the cell line. These cell lines may provide a useful model for studying mechanisms of metastasis of human lung cancer. Less
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