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Negative Feedback Regulation of Phosphatidylinositol 3‐Kinase/Akt Pathway by Over‐Expressed Cyclooxygenase‐2 in Human Epidermal Cancer Cells
Author(s) -
Takeda Koichiro,
Kanekura Takuro,
Kanzaki Tamotsu
Publication year - 2004
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.2004.tb00547.x
Subject(s) - hacat , protein kinase b , pi3k/akt/mtor pathway , ly294002 , phosphatidylinositol , phosphorylation , kinase , microbiology and biotechnology , cancer research , biology , cancer cell , signal transduction , chemistry , cell culture , cancer , genetics
While enhanced expression of cyclooxygenase (COX)‐2 has been observed in human skin epidermal cancer, the mechanisms underlying COX‐2 expression have not been completely elucidated. Recently, a role for the phosphatidylinositol‐3 (PI3) kinase pathway in COX‐2 expression has attracted attention. We investigated COX‐2 expression, PI3 kinase activity, and the phosphorylation level of Akt, a downstream effector of PI3 kinase, in the human skin cancer cell line HSC‐5. Compared to the nontumorigenic keratinocyte HaCaT, in HSC‐5 cells, COX‐2 protein expression and PI3 kinase activity were increased. The PI3 kinase inhibitor LY294002 reduced COX‐2 expression in HSC‐5 cells and, contrary to our expectation, the phosphorylation of Akt was significantly decreased. The expression of Bcl‐2, which is regulated by Akt, was reduced, and apoptosis was induced in HSC‐5 cells compared to HaCaT cells. COX‐2 inhibitor NS398 up‐regulated Akt phosphorylation. These results imply that constitutively over‐expressed COX‐2 down‐regulates the Akt phosphorylation through a negative feedback mechanism.