@article{oai:dmu.repo.nii.ac.jp:00000321,
 author = {藤井, 陽一朗 and 島田, 忠人 and Fujii, Yoichiro and Shimada, Tadahito},
 issue = {1},
 journal = {Dokkyo journal of medical sciences},
 month = {Mar},
 note = {乳癌由来細胞株MCF-7でエストロゲン誘導遺伝子として見出されたTFF1は,生理的には胃粘膜に発現し重要な粘膜防御因子として機能している.本研究では,胃癌由来細胞株MKN45を用い,胃におけるTFF1発現調節機構について検討した.MCF-7ではTFF1発現はエストロゲン依存的であったが,MKN45ではTFF1の発現はエストロゲン非感受性であり,TFF1遺伝子プロモーター上のエストロゲン応答配列よりもさらに近位側の配列が,MKN45におけるTFF1発現に大きな影響を与えていた.MKN45にもエストロゲン受容体(ERα,ERβ)の発現は認められたが,MCF-7と比べるとERαの発現レベルが低く,ERαを強制的に発現させるとMKN45でもTFF1発現がエストロゲン感受性となった.胃粘膜でのTFF1発現は粘膜損傷時に上昇することが知られているので,このような誘導性のTFF1発現機構を検討する目的でphorbol ester (TPA),TNF-αの影響をみたところ,TPAはAP-1を介して,TNF-αはNF-κBを介してTFF1の発現を上昇させることが示唆された.これらの結果より,胃粘膜上皮細胞ではTFF1発現はエストロゲン非依存性であり,また,AP-1やNF-κBが誘導性の発現調節に関与していると考えられた., Trefoil factor family 1 (TFF1) is a protease-resistant polypeptide expressed at a high level in gastric epithelial cells and plays a critical role in the defense and repair of gastric mucosa. In the present study, we examined the regulatory mechanisms of gastric TFF1 expression using a gastric cancer cell line, MKN45. Since TFF1 was originally discovered as an estrogen-inducible gene in a breast cancer cell line, MCF-7, MCF-7 was also examined for comparison. The promoter sequence of human TFF1 gene (-953 to +34) was cloned into pGL3 basic vector to make a TFF1 reporter gene and several deletion mutant reporters were also made. Endogenous TFF1 mRNA expression was analyzed by real-time quantitative RT- PCR. In MCF- 7 cells, basal TFF1 expression was dependent on the presence of an estrogen-responsive element (ERE) (-406), while deletion of ERE had no significant effect on the reporter gene expression in MKN45 cells. In MKN45 cells, deletion of more proximal region (-393 to -365) significantly affected the reporter gene expression. Compared to estrogen receptor β (ER β), the expression level of estrogen receptor α (ER α) was low in MKN45 cells and we found that TFF1 expression became estrogen-sensitive when ER a was overexpressed in MKN45 cells. Phorbol-12-miristate-13-acetate (TPA) and tumor necrosis factor-α (TNF-α) up-regulated the expression of endogenous TFF1 mRNA and TFF1 reporter genes. A series of reporter gene experiments suggested that AP-1 site (-338) and NF-κB sites (-251, -230) are involved in the action of TPA and TNF-α, respectively. These results suggest that, compared to MCF-7 cells, the basal TFF1 expression is differently regulated in gastric epithelial cells, and that up-regulation of TFF1 expression, which is often observed at the site of gastric mucosal lesions, may be mediated by AP-1 and/or NF-κB., 原著, Original},
 pages = {29--37},
 title = {胃粘膜上皮細胞におけるtrefoil factor family 1 (TFF1)発現に影響を与える因子に関する検討},
 volume = {32},
 year = {2005},
 yomi = {フジイ, ヨウイチロウ and シマダ, タダヒト}
}