| Item type |
文献 / Documents(1) |
| 公開日 |
2021-04-22 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版社版DOI |
|
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|
関連識別子 |
https://doi.org/10.1002/prp2.441 |
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関連名称 |
10.1002/prp2.441 |
| 出版タイプ |
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出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| タイトル |
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|
タイトル |
Cellular density‐dependent increases in HIF‐1α compete with c‐Myc to down‐regulate human EP4 receptor promoter activity through Sp‐1‐binding region |
| 著者 |
セイラ, ナオフミ
ヤマガタ, カズユキ
福島, 圭穣
アラキ, ユミ
クラタ, ナオキ
ヤナギサワ, ナオキ
マシモ, マサト
ナカムラ, ヒロユキ
Regan, John W.
ムラヤマ, トシヒコ
藤野, 裕道
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| 抄録 |
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内容記述 |
The up‐regulated expression of E‐type prostanoid (EP) 4 receptors has been implicated in carcinogenesis; however, the expression of EP4 receptors has also been reported to be weaker in tumor tissues than in normal tissues. Indeed, EP4 receptors have been suggested to play a role in the maintenance of colorectal homeostasis. This study aimed to examine the underlying mechanisms/reasons for why inconsistent findings have been reported regarding EP4 receptor expression levels in homeostasis and carcinogenesis by focusing on cellular densities. Thus, the human colon cancer HCA‐7 cells, which retain some functional features of normal epithelia, and luciferase reporter genes containing wild‐type or mutated EP4 receptor promoters were used for elucidating the cellular density‐dependent mechanisms about the regulation of EP4 receptor expression. In silico analysis was also utilized for confirming the relevance of the findings with respect to colon cancer development. We here demonstrated that the expression of EP4 receptors was up‐regulated by c‐Myc by binding to Sp‐1 under low cellular density conditions, but was down‐regulated under high cellular density conditions via the increase in the expression levels of HIF‐1α protein, which may pull out c‐Myc and Sp‐1 from DNA‐binding. The tightly regulated EP4 receptor expression mechanism may be a critical system for maintaining homeostasis in normal colorectal epithelial cells. Therefore, once the system is altered, possibly due to the transient overexpression of EP4 receptors, it may result in aberrant cellular proliferation and transformation to cancerous phenotypes. However, at the point, EP4 receptors themselves and their mediated homeostasis would be no longer required. |
| キーワード |
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|
主題 |
c-Myc |
| キーワード |
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|
主題 |
colorectal cancer |
| キーワード |
|
|
主題 |
EP4 receptors |
| キーワード |
|
|
主題 |
HIF-1α |
| キーワード |
|
|
主題 |
homeostasis |
| キーワード |
|
|
主題 |
Sp-1 |
| 書誌情報 |
en : Pharmacology Research & Perspectives
巻 6,
号 6,
p. e00441,
発行日 2018-11-11
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
|
収録物識別子 |
20521707 |
| 出版者 |
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|
出版者 |
John Wiley & Sons |
| 出版者 |
|
|
出版者 |
British Pharmacological Society |
| 出版者 |
|
|
出版者 |
American Society for Pharmacology and Experimental Therapeutics |
| 権利情報 |
|
|
権利情報 |
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| EID |
|
|
識別子 |
351286 |
| 言語 |
|
|
言語 |
eng |
prp_6_6_e00441.pdf (3.1 MB)
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