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Induction of 12‐lipoxygenase expression by transforming growth factor‐α in human epidermoid carcinoma A431 cells
Author(s) -
Chen Lei-Chin,
Chen Ben-Kuen,
Liu Yi-Wen,
Chang Wen-Chang
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00865-0
Subject(s) - transfection , epidermoid carcinoma , arachidonate 5 lipoxygenase , microbiology and biotechnology , transforming growth factor , luciferase , reporter gene , biology , squamous carcinoma , a431 cells , lipoxygenase , messenger rna , promoter , gene expression , gene , chemistry , enzyme , biochemistry , oncogene , carcinoma , genetics , cell cycle , arachidonic acid
Transforming growth factor‐α (TGF‐α) increased the expression of 12‐lipoxygenase activity in a time‐dependent manner in human epidermoid carcinoma A431 cells. The increase of 12‐lipoxygenase activity was accompanied by an increase in 12‐lipoxygenase mRNA. The effect of TGF‐α on the promoter activation of 12‐lipoxygenase gene was analyzed by using the luciferase fusion vectors. A dose‐dependent effect of TGF‐α on the reporter activity was observed, which paralleled with its effect on enzyme activity. Transient transfection with a series of 5′‐deleted constructs showed that the 5′‐flanking region spanning from −224 to −100 bp from translation starting site played an important role for TGF‐α response. Site‐directed mutagenesis and gel mobility shift assay indicated that two Sp1 binding sequences residing at −158 to −150 bp and −123 to −114 bp were responsible for the TGF‐α in activation of human 12‐lipoxygenase gene transcription. Expression of Sp1, but not Sp3, stimulated the promoter activity of 12‐lipoxygenase in SL2 cells, indicating that the binding of Sp1 with Sp1 binding sequences played a significant role in the regulation of 12‐lipoxygenase gene.