| Item type |
学術雑誌論文 / Journal Article_02(1) |
| 公開日 |
2009-04-24 |
| タイトル |
|
|
タイトル |
Hypoxia-independent overexpression of hypoxia-inducible factor 1α as an early change in mouse hepatocarcinogenesis. |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ |
journal article |
| その他（別言語等）のタイトル |
|
|
その他のタイトル |
Hypoxia-independent overexpression of HIF-1α as an early change in mouse hepatocarcinogenesis. |
|
言語 |
en |
| 著者 |
田中, 宏樹
Yamamoto, M
Hashimoto, N
Miyakoshi, M
Tamakawa, S
Yoshie, M
Tokusashi, Y
Yokoyama, K
Yaginuma, Y
Ogawa, K
|
| 著者 ローマ字 |
|
|
|
Tanaka, Hiroki |
| 著者 ローマ字 |
|
|
|
en |
| 書誌情報 |
Cancer Research
巻 66,
号 23,
p. 11263-11270,
発行日 2006-12-01
|
| ISSN |
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|
収録物識別子タイプ |
ISSN |
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収録物識別子 |
0008-5472 |
| DOI |
|
|
関連タイプ |
isVersionOf |
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|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1158/0008-5472.CAN-06-1699 |
| リンクURL |
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内容記述タイプ |
Other |
|
内容記述 |
http://dx.doi.org/10.1158/0008-5472.CAN-06-1699 | http://dx.doi.org/10.1158/0008-5472.CAN-06-1699 |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
HIF-1 is involved in tumor progression/metastasis and activated in various cancers. Here we show that HIF-1α, which plays a major role in HIF-1 activation, is over-expressed in preneoplastic hepatocytic lesions from a very early stage during hepatocarcinogenesis in mice and man. Transcriptional targets of HIF-1, such as VEGF, glut-1, c-met and Igf-2, were also over-expressed in mice lesions. HIF-1α expression was independent of hypoxia, because pimonidazole immunostaining was negative in the mouse lesions after treatment with pimonidazole. On the other hand, Akt, the pathway of which can up-regulate HIF-1α expression, was activated in the mouse lesions, while HIF-1α was markedly downregulated in the mouse HCC cell lines after treatment with a PI3 kinase (PI3K) inhibitor, LY294002, indicating that HIF-1α expression is dependent on PI3K/Akt signaling. Conversely, HIF-1α knockdown by siRNA in the HCC cell line resulted in decreased expression of activated Akt together with the HIF-1 target genes, indicating that Akt activation is reversely dependent on HIF-1 activation. Treating the HCC cells with Igf-2 upregulated both phospho-Akt and HIF-1α, while inhibition of Igf-2 by the neutralizing Igf-2 antibody downregulated them both, suggesting that Igf-2 may, at least in part, mediate the activation of Akt and HIF-1α. However, Akt was not activated by Igf-2 or EGF in the HIF-1α knockdown cells, indicating that expression of the HIF-1 target genesis necessary for the Akt activation. These findings suggest that the reciprocal activation of PI3K/Akt signaling and HIF-1α may be important in progression of hepatocarcinogenesis. |
| 注記 |
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内容記述タイプ |
Other |
|
注記 |
author |
|
言語 |
en |
| 資源タイプ |
|
|
内容記述タイプ |
Other |
|
資源タイプ |
text |
| 著者版フラグ |
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出版タイプ |
AM |
| フォーマット |
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内容記述タイプ |
Other |
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内容記述 |
application/pdf |
| ID(XooNIps) |
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|
17145871 |
| 閲覧数(XooNIps) |
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| ダウンロード数(XooNIps) |
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|
1110 |
2039.pdf (4.5 MB)
