Activation of serum response factor in the liver of Long-Evans Cinnamon (LEC) rat.
We have studied the DNA binding activities of transcription factors in the liver of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. Owing to a genetic defect, this strain of rats accumulates excessive copper in the liver and develops severe hepatitis and hepatocellular carcinoma. We found that the DNA binding activity of the serum response factor (SRF) was higher in the liver of LEC rats (approximately 2-fold) than in that of Wistar rats. There was a close correlation between the intensity of the activity and the concentrations of copper in the nuclear protein. The DNA binding activity of Sp1, on the other hand, showed similar levels in both LEC and Wistar rats. SRF may play an important role in the development of hepatocellular carcinoma in LEC rats by mediating the proto-oncogene c-fos induction. We suggest that the copper in nuclear protein may be involved in the activation of SRF.
Maeda
Y
Y
Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Taira
T
T
Haraguchi
K
K
Hirose
K
K
Kazusaka
A
A
Fujita
S
S
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D003300:Copper / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000209:etiology; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D026362:Serum Response Factor; D013045:Species Specificity; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D003300:Copper