Anoxia/reoxygenation down-regulates the expression of E-cadherin in human colon cancer cell lines.
The E-cadherin-mediated cell-cell adhesiveness is a critical factor for carcinoma cell invasion and metastasis. Anoxia/reoxygenation is known to occur in cancer tissues. In this study, we investigated whether anoxia/reoxygenation induces the down-regulation of E-cadherin expression in the human colon cancer cell lines HT-29, and SW1116. Colon cancer cells were exposed to anoxia (2 h) followed by reoxygenation (4-46 h). The subsequent expression of E-cadherin on the cell surface was examined by immunocytochemistry and enzyme-linked immunosorbent assays, the total amount of E-cadherin protein was examined by Western blotting, and the E-cadherin mRNA level was examined by a real-time polymerase chain reaction assay. The expression of E-cadherin on the cell surface and the total amount of E-cadherin protein were transiently reduced after anoxia/reoxygenation. On the other hand, the E-cadherin mRNA level was not decreased during reoxygenation. Pretreatment with actinomycin D or reagents that interfere with the activation of NF-kappaB significantly attenuated the down-regulation of E-cadherin, which implicated a role for the de novo protein synthesis. These results indicate that anoxia/reoxygenation induces a transient reduction of E-cadherin expression in human colon cancer cells through NF-kappaB dependent transcriptional pathway.
Kokura
Satoshi
S
Molecular Gastroenterology and hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. s-kokura@mpd.biglobe.ne.jp
Yoshida
Norimasa
N
Imamoto
Eiko
E
Ueda
Miho
M
Ishikawa
Takeshi
T
Uchiyama
Kazuhiko
K
Kuchide
Masashi
M
Naito
Yuji
Y
Okanoue
Takeshi
T
Yoshikawa
Toshikazu
T
D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D019073:HT29 Cells; D006801:Humans; D010100:Oxygen / Q000378:metabolism*; D014158:Transcription, Genetic
D015820:Cadherins; D003609:Dactinomycin; D010100:Oxygen