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

Abstract

Lung resistancerelated 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.

Proteomic Differences Between Hepatocellular Carcinoma and Nontumorous Liver Tissue Investigated by a Combined Gel-based and Label-free Quantitative Proteomics Study

“…The relatively large variance of expression levels that was detected within the HCC experimental groups is in line with previous observations and is caused by an interindividual heterogeneity of MVP expression in liver tissue that has already been described (81). In summary, we conclude that MVP is a robust HCC diagnostic biomarker candidate that can be used to distinguish normal liver and HCC tumor tissues irrespective of the underlying liver disease or tumor characteristics.…”

“…However, in case of liver carcinomas a variable expression has been reported (81). Contrary, our recent results clearly verify an over-expression of MVP in tumorous HCC tissue.…”

Vaults and the major vault protein: Novel roles in signal pathway regulation and immunity

“…Additionally, it must be mentioned that several proteins encoded by very important (proto)oncogenes (EGF/EGFR, Src, cJun), but also tumor-suppressor genes (e.g. PTEN, [35,36,136] or maintain the high MVP expression already present in the respective normal tissues [117,118,157]. Accordingly, in some tumor types MVP levels correlated with a worse prognosis not related to chemotherapy failure [37].…”

NORE1B, a candidate tumor suppressor, is epigenetically silenced in human hepatocellular carcinoma

“…We established new HCC-derived cell lines, which are in early passages and well authenticated by complete clinical data as well as extensive biological and genetic investigations of both tumor and cell line derived thereof. All lines were maintained, as described [24]. 5·10 6 cells were treated once per day for 4 days with 0.5 lM 5-aza-cytidine (Sigma, Germany).…”

“…Subsequently cells were kept for 2-3 days in 5-aza-cytidine-free medium, harvested, and subjected to RT-PCR and immunoblotting. DNA and RNA were extracted from microdissected tissue samples and the cell-lines as described [21,24].…”