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Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells
| Title: | Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells |
| Authors: | Niizeki, Hiroto Browse this author | | Kobayashi, Masanobu Browse this author | | Horiuchi, Iori Browse this author | | Akakura, Nobuaki Browse this author | | Chen, Jian Browse this author | | Wang, Jingxin Browse this author | | Hamada, Jun-ichi Browse this author | | Seth, Prem Browse this author | | Katoh, Hiroyuki Browse this author | | Watanabe, Hideomi Browse this author | | Raz, Avraham Browse this author | | Hosokawa, Masuo Browse this author |
| Keywords: | hypoxia | | AMF | | motility | | HIF-1 | | metastasis |
| Issue Date: | 17-Jun-2002 |
| Publisher: | Nature Publishing Group |
| Journal Title: | British Journal of Cancer |
| Volume: | 86 |
| Issue: | 12 |
| Start Page: | 1914 |
| End Page: | 1919 |
| Publisher DOI: | 10.1038/sj.bjc.6600331 |
| Abstract: | 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. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/11317 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 小林 正伸
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