title: Characteristic upregulation of glucose-regulated protein 78 in an early lesion negative for hitherto established cytochemical markers in rat hepatocarcinogenesis.
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.
authors.forename: Tokuo
authors.initials: T
authors.lastname: Sukata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uwagawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ozaki
authors.forename: Kayo
authors.initials: K
authors.lastname: Sumida
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kushida
authors.forename: Anna
authors.initials: A
authors.lastname: Kakehashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Kaori
authors.initials: K
authors.lastname: Miyata
authors.forename: Keiko
authors.initials: K
authors.lastname: Ogata
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima