| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Hypoxia-inducible factor-1α, HIF-1α, is a transcriptional factor that regulates genes involved in the response to hypoxia. To clarify its roles in tumour growth and progression, we established HIF-1α-overexpressing renal cell carcinoma VMRC cells (VMRC-HIF1α cells) and bladder cancer EJ cells (EJ-HIF1α cells) and compared their characteristics with VMRC-neo and EJ-neo control cells. In vitro studies showed that overexpression of HIF-1α in both VMRC and EJ cells relieves the contact inhibition of cell proliferation and renders these cells resistant to hypoxic stress. We further examined in vivo tumourigenicity in nude mice. All four types of cancer cells (VMRC-neo cells, VMRC-HIF1α cells, EJ-neo cells, and EJ-HIF1α cells) formed tumours in nude mice, and the size of VMRC-HIF1α cell-derived xenografts was much larger than that of VMRC-neo cells. Although HIF-1α overexpression did not affect the size of EJ cell-derived xenografts, histological examination showed that there was only a small area of necrosis in the EJ-HIF1α cell-derived xenografts whereas a large area of central necrosis was observed in the EJ-neo cell-dereived xenografts. It was also found that HIF-1α overexpression increased intratumoural microvessel density in the xenografts. These results suggest that HIF-1α may play important roles in bladder and renal cancer angiogenesis, growth and progression.
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