title: Expression of the lung resistance-related protein in human and rat hepatocarcinogenesis.
abstract: 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.
authors.affiliation: Institute of Cancer Research, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Raidl
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Rolf
authors.initials: R
authors.lastname: Schulte-Hermann
authors.forename: Daniela
authors.initials: D
authors.lastname: Kandioler-Eckersberger
authors.forename: Sonja
authors.initials: S
authors.lastname: Kappel
authors.forename: Fritz
authors.initials: F
authors.lastname: Wrba
authors.forename: Michael
authors.initials: M
authors.lastname: Micksche
authors.forename: Bettina
authors.initials: B
authors.lastname: Grasl-Kraupp
mesh_terms: D000236:Adenoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics / Q000378:metabolism*; D000099187:Major Vault Protein
chemical_list: D005982:Glutathione Transferase; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein