Characteristic upregulation of glucose-regulated protein 78 in an early lesion negative for hitherto established cytochemical markers in rat hepatocarcinogenesis |
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| Authors: | Sukata Tokuo Uwagawa Satoshi Ozaki Keisuke Sumida Kayo Kushida Masahiko Kakehashi Anna Wanibuchi Hideki Miyata Kaori Ogata Keiko Fukushima Shoji |
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| Institution: | 1.Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 1–98, 3-chome, Kasugade-Naka, Konohana-ku, Osaka 554-8558, Japan;2.Department of Pathology, Osaka City University Medical School, 1–4–3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan;3.Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015, Japan |
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| Abstract: | Previously, we reported α(2)-macroglobulin (α(2)M) 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. |
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| Keywords: | molecular marker glucose-regulated protein 78 α2-macroglobulin preneoplastic lesion rat hepatocarcinogenesis |
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