Expression of the lung resistance-related protein in human and rat hepatocarcinogenesis

Lung resistance-related protein (LRP) plays an important role in chemoresistance of tumor cells probably by altering nuclear-cytoplasmic transport processes. We analyzed the association between LRP expression and hepatocarcinogenesis in humans and rats by RT-PCR, immunoblotting, and immunohistochemi...

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Published in:American journal of physiology: Gastrointestinal and liver physiology 2002-11, Vol.283 (5), p.G1117-G1124
Main Authors: Raidl, Maria, Berger, Walter, Schulte-Hermann, Rolf, Kandioler-Eckersberger, Daniela, Kappel, Sonja, Wrba, Fritz, Micksche, Michael, Grasl-Kraupp, Bettina
Format: Article
Language:English
Subjects:
Adenoma - metabolism
Adult
Aged
Animals
Carcinoma, Hepatocellular - metabolism
Female
Glutathione Transferase - metabolism
Humans
Liver - metabolism
Liver Neoplasms - metabolism
Male
Middle Aged
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Precancerous Conditions - metabolism
Rats
Rats, Wistar
Reference Values
RNA, Messenger - metabolism
Tumor Cells, Cultured
Vault Ribonucleoprotein Particles - genetics
Vault Ribonucleoprotein Particles - metabolism
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Summary:Lung resistance-related protein (LRP) plays an important role in chemoresistance of tumor cells probably by altering nuclear-cytoplasmic transport processes. We analyzed the association between LRP expression and hepatocarcinogenesis in humans and rats by RT-PCR, immunoblotting, and immunohistochemistry. LRP was found in hepatocytes and bile epithelia of normal human and rat liver showing distinct interindividual variations. In human tissues, the LRP expression levels of dysplastic liver nodules, hepatocellular adenomas, and carcinomas were highly variable, including decreased but also distinctly increased staining intensities. Mean expression levels, however, were comparable to the surrounding tissue. Considerable levels of LRP mRNA and protein were also found in human hepatoma cell lines. To study LRP expression from the beginning of hepatocarcinogenesis onward, rats were subjected to a tumor initiation/promotion protocol leading to preneoplastic hepatocytes present as single cells or multicellular clones, followed by adenoma and carcinoma. All of the (pre)neoplastic rat liver lesions expressed, comparable to the surrounding tissue, considerable amounts of LRP. We conclude that LRP might be one mechanism involved in the intrinsically high but variable chemoresistance of normal and (pre)neoplastic hepatocytes.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.00195.2002