Characteristic Upregulation of Glucose-Regulated Protein 78 in an Early Lesion Negative for Hitherto Established Cytochemical Markers in Rat Hepatocarcinogenesis

• Published in: Journal of Toxicologic Pathology 2009, Vol.22(4), pp.281-288
• Main Authors: Sukata, Tokuo, Uwagawa, Satoshi, Ozaki, Keisuke, Sumida, Kayo, Kushida, Masahiko, Kakehashi, Anna, Wanibuchi, Hideki, Miyata, Kaori, Ogata, Keiko, Fukushima, Shoji
• Format: Article
• Language: English
• Subjects: glucose-regulated protein 78; molecular marker; Original; preneoplastic lesion; rat hepatocarcinogenesis; α2-macroglobulin
• ISSN: 0914-9198; 1881-915X; 1347-7404
• DOI: 10.1293/tox.22.281

Previously, we reported α2-macroglobulin (α2M) to be a novel marker characteristic of rat hepatocellular preneoplastic and neoplastic lesions negative for hitherto well-established markers. In the present study, we further examined other candidate markers with specificity for the same type of lesions. Glutathione S-transferase-placental form (GST-P)-negative hepatocellular altered foci (HAF) were generated using a two-stage (initiation and promotion) carcinogenesis protocol with N,N-diethylnitrosamine (DEN) and either Wy-14,643 or clofibrate, two peroxisome proliferators. Microarray analysis using total RNAs isolated from laser-microdissected GST-P-negative HAF (amphophilic cell foci) and adjacent normal tissues was conducted along with immunohistochemistry and real-time RT-PCR. Staining for glucose-regulated protein 78 (GRP78) was detected in GST-P-negative HAF and hepatocellular adenomas, and slightly increased GRP78 mRNA expression was observed in the lesions by real-time RT-PCR analysis. Thus, an early increase of GRP78 expression in hepatocarcinogenesis is likely a feature of the amphophilic subset of HAF.