Lc. Chen et al., Induction of 12-lipoxygenase expression by transforming growth factor-alpha in human epidermoid carcinoma A431 cells, FEBS LETTER, 455(1-2), 1999, pp. 105-110
Transforming growth factor-alpha (TGF-alpha) increased the expression of 12
-lipoxygenase activity in a time-dependent manner in human epidermoid carci
noma A431 cells. The increase of 12-lipoxygenase activity was accompanied b
y an increase in 12-lipoxygenase mRNA. The effect of TGF-alpha on the promo
ter activation of 12-lipoxygenase gene was analyzed by using the luciferase
fusion vectors. A dose-dependent effect of TGF-alpha on the reporter activ
ity was observed, which paralleled with its effect on enzyme activity. Tran
sient transfection with a series of 5'-deleted constructs showed that the 5
'-flanking region spanning from -224 to -100 bp from translation starting s
ite played an important role for TGF-alpha response. Site-directed mutagene
sis and gel mobility shift assay indicated that two Sp1 binding sequences r
esiding at -158 to -150 bp and -123 to -114 bp were responsible for the TGF
-alpha in activation of human 12-lipoxygenase gene transcription. Expressio
n 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. (C) 1
999 Federation of European Biochemical Societies.