Cytokeratin 8/18 as a new marker of mouse liver preneoplastic lesions

Journal Article · Fri Jan 01 04:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.09.013· OSTI ID:21344825

Kakehashi, Anna; Kato, Ayumi; Inoue, Masayo; Ishii, Naomi ^[1]; Okazaki, Etsuko ^[2]; Wei, Min ^[1]; Tachibana, Taro ^[2]; Wanibuchi, Hideki ^[1]

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1. Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)
2. Department of Bioengineering, Graduate School of Engineering, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585 (Japan)

To search for a reliable biomarker of preneoplastic lesions arising early in mouse hepatocarcinogenesis the proteomes of microdissected basophilic foci, hepatocellular adenomas (HCAs), carcinomas (HCCs) and normal-appearing liver of B6C3F1 mice initiated with diethylnitrosamine (DEN) were analysed on anionic (Q10) surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip arrays. Significant overexpression of cytokeratin 8 (CK8; m/z 54, 565), cytokeratin 18 (CK18; m/z 47,538) proteins was found in basophilic foci as well as in HCAs and HCCs. Furthermore, immunohistochemistry demonstrated profound overexpression of CK8 and CK18 proteins (CK8/18) in all basophilic foci, mixed cell type foci, HCAs and HCCs in B6C3F1 and C57BL/6J mice initiated with DEN. A strong correlation between CK8/18-positive foci development and multiplicity of liver tumors in B6C3F1 and C57Bl/6J mice was further observed. Moreover, formation of CK8 and CK18 complexes due to CK8 phosphorylation at Ser73 and Ser431 was found to be strongly associated with neoplastic transformation of mice liver basophilic foci. Elevation of CK8/18 was strongly correlated with induction of cell proliferation in basophilic foci and tumors. In conclusion, our data imply that CK8/18 is a novel reliable marker of preneoplastic lesions arising during mouse hepatocarcinogenesis which might be used for prediction of tumor development and evaluation of environmental agents as well as drugs and food additives using mouse liver tests.

• OSTI ID: 21344825
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 242; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADENOMAS
ANIMALS
BIOLOGICAL MARKERS
BODY
CARCINOMAS
CELL PROLIFERATION
CHEMICAL REACTIONS
DIGESTIVE SYSTEM
DISEASES
FORECASTING
GLANDS
KERATIN
LIVER
MAMMALS
MASS SPECTROSCOPY
MICE
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
PHOSPHORYLATION
PROTEINS
RODENTS
SCLEROPROTEINS
SPECTROSCOPY
TIME-OF-FLIGHT METHOD
VERTEBRATES