Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells
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概要
- 論文の詳細を見る
The incidence of distant metastases is higher in the tumors with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumor cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumor cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor (AMF) mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. AMF inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1α (HIF-1α), we established HIF-1α-transfectants and dominant negative HIF-1α-transfectants. Transfection with HIF-1α and dominant-negative HIF-1α enhanced and suppressed the expression of AMF/PHI/NL mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced AMF/PHI/NL mRNA expression and that the disruption of the HIF-1 pathway may be an effective treatment for metastasis.
- Nature Publishing Groupの論文
- 2002-06-17
著者
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Hosokawa M
Division Of Pathology Cancer Institute Hokkaido University School Of Medicene
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Hamada Jun-ichi
北海道大学 歯学研究科口腔健康科学高齢者歯科学
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Hamada J
Hokkaido Univ. Sapporo
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Kobayashi M
Department Of Public Health Social Medicine And Medical Informatics Ehime University Graduate School
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