Development of glutathione S‐transferase‐P‐negative foci accompanying nuclear factor‐erythroid 2‐related factor 2 expression during early stage of rat hepatocarcinogenesis

Glutathione S‐transferase P (GST‐P), a marker for rat hepatic preneoplastic lesions, is suggested to bind to Jun N‐terminal kinase (JNK) to repress stress response, and GST‐P gene expression is regulated by a transcription factor, nuclear factor‐erythroid 2‐related factor 2 (Nrf2). In this study, we...

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Published in:Cancer science 2008-03, Vol.99 (3), p.497-501
Main Authors: Fan, Yang, Shimizu, Takeshi, Yamada, Toshiyuki, Nanashima, Naoki, Akita, Miki, Asano, Jumpei, Tsuchida, Shigeki
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Gastroenterology. Liver. Pancreas. Abdomen
Glutathione Transferase - genetics
Glutathione Transferase - metabolism
Immunohistochemistry
Liver Neoplasms, Experimental - enzymology
Liver Neoplasms, Experimental - genetics
Liver Neoplasms, Experimental - metabolism
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Mitogen-Activated Protein Kinase 9 - metabolism
NF-E2-Related Factor 2 - metabolism
Original
p38 Mitogen-Activated Protein Kinases - metabolism
Rats
Rats, Sprague-Dawley
Tumors
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Summary:Glutathione S‐transferase P (GST‐P), a marker for rat hepatic preneoplastic lesions, is suggested to bind to Jun N‐terminal kinase (JNK) to repress stress response, and GST‐P gene expression is regulated by a transcription factor, nuclear factor‐erythroid 2‐related factor 2 (Nrf2). In this study, we examined by immunohistochemistry whether JNK2, p38 mitogen‐activated protein kinase, and Nrf2 were expressed in GST‐P‐positive foci induced by the Solt–Farber protocol. At 2 weeks after partial hepatectomy, all GST‐P‐positive foci were negative for p38, and 86.4 ± 5.6% and 64.7 ± 6.3% of GST‐P‐positive foci were negative for JNK2 and Nrf2, respectively. Western blot analysis showed decreased p38 mitogen‐activated protein kinase and JNK2 expression in livers treated with the protocol. In immunohistochemistry, besides GST‐P‐positive foci, GST‐P‐negative foci were detected as p38‐negative foci in the surrounding tissues positive for p38. In contrast to GST‐P‐positive foci, most GST‐P‐negative foci showed enhanced Nrf2 expression. The number of GST‐P‐negative foci was 76 ± 18/10 mm2 of liver section at 2 weeks, but was undetectable at 1 week. The area of GST‐P‐negative foci was 0.09 ± 0.05 mm2, smaller than that of GST‐P‐positive ones (0.29 ± 0.23). After treatment with carbon tetrachloride, small vacuoles due to liver injury were frequently observed inside GST‐P‐negative foci but less frequently in GST‐P‐positive foci. However, this treatment resulted in expression of JNK2, p38, and Nrf2 in both foci. These results showed development of GST‐P‐negative foci during the early stage of hepatocarcinogenesis and suggested that Nrf2 is not responsible for GST‐P expression in rat hepatic preneoplastic foci. (Cancer Sci 2008; 99: 497–501)
ISSN:1347-9032
1349-7006
1349-7006
DOI:10.1111/j.1349-7006.2007.00703.x