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The mechanism of specific expression of glutathione transferase P gene during hepatocarcinogenesis of the rat has been investigated by cloning the gene and determining the upstream regulatory sequences. Two enhancers and a silencer are located within 3 kb upstream of the promoter. The stronger enhancer designated GPEI has two TPA (12-O-tetradecanoyl phorbol 13-acetate)-response element (TRE)-like sequences arranged in a palindrome at a 3 base pairs spacing. This special combination was found to form a very strong enhancer which could act efficiently even in F9 cells where the collagenase enhancer with a singlet TRE cannot work due to the low c-jun content. Whether this structure is operating with a very low concentration of c-jun/c-fos heterodimer or with any other proteins remains to be determined. These findings suggest that new and more efficient enhancers evolve by a combination of basic enhancer elements. The silencer region consists of several sequences that can bind specific protein(s) and works cooperatively.
M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
March 1993,
Proceedings of the National Academy of Sciences of the United States of America,
M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
December 2006,
Proceedings of the Japan Academy. Series B, Physical and biological sciences,
M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
June 2004,
Cancer letters,
M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
June 2007,
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M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
January 2005,
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M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
January 1996,
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M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
June 2004,
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M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
March 1993,
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M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
September 1992,
Biochemical and biophysical research communications,
M Muramatsu, and
A Okuda, and
S Morimura, and
S Osada, and
M B Diccianni, and
M Imagawa
January 1996,
Journal of cancer research and clinical oncology,
