ArticleToxicology and applied pharmacology2009
Cytokeratin 8/18 overexpression and complex formation as an indicator of GST-P positive foci transformation into hepatocellular carcinomas.
Article in Toxicology and applied pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 38 citations in OpenAlex.
- An Update of Immunohistochemistry in Hepatocellular Carcinoma.Diagnostics (Basel, Switzerland) · 2025Review
- The application of cytokeratin-18 as a biomarker for drug-induced liver injury.Archives of toxicology · 2021Review
- Article
- Role of Glypican-3 in the growth, migration and invasion of primary hepatocytes isolated from patients with hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- Therapeutic effects of hepatocyte growth factor-overexpressing dental pulp stem cells on liver cirrhosis in a rat model.Scientific reports · 2017Article
- Altered methylation of specific DNA loci in the liver ofFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Cytokeratin-18 in Diagnosis of HCC in Patients with Liver CirrhosisAsian Pacific journal of cancer prevention : APJCP · 2017Article
- Hepatocellular adenoma with severe fatty change in a male Spontaneously Diabetic Torii rat.Journal of toxicologic pathology · 2017Article
- Progression of Hepatic Adenoma to Carcinoma inOxidative medicine and cellular longevity · 2017Article
- Phosphorylation and Reorganization of Keratin Networks: Implications for Carcinogenesis and Epithelial Mesenchymal Transition.Biomolecules & therapeutics · 2015Review
- Apoptotic effects of dipyrido [3,2-a:2',3'-c] phenazine (dppz) Au(III) complex against diethylnitrosamine/phenobarbital induced experimental hepatocarcinogenesis in rats.Molecular biology reports · 2014Article
- Valerian inhibits rat hepatocarcinogenesis by activating GABA(A) receptor-mediated signaling.PloS one · 2014Article
- Article
- Targeted proteomics of isolated glomeruli from the kidneys of diabetic rats: sorbin and SH3 domain containing 2 is a novel protein associated with diabetic nephropathy.Experimental diabetes research · 2011Article
- Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis.World journal of gastroenterology · 2009Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Screening of the proteome of microdissected glutathione S-transferase placental form (GST-P) positive foci and normal-appearing liver on anionic (Q10), and cationic (CM10) surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip arrays demonstrated significant overexpression of cytokeratin 8 (CK8; m/z 54,020), cytokeratin 18 (CK18; m/z 47,760), microsomal cytochrome 5A (m/z 15,224) and histone type 2 H2aa3 (m/z 15,964) in the livers of rats initiated with diethylnitrosamine (DEN) followed by 10 weeks on phenobarbital (PB) at a dose of 500 ppm. Furthermore, formation of CK8 and CK18 complexes due to CK8 phosphorylation at Ser73 and Ser431 was found to be strongly associated with promotion of hepatocarcinogenesis by PB and the development of hepatocellular carcinomas. The data were confirmed by immunohistochemistry and real-time Q-PCR and profound overexpression of CK8 and CK18 (CK8/18) proteins and mRNAs were detected in several large size GST-P positive foci and liver tumors. A strong correlation between CK8/18 positive foci development and multiplicity of hepatocellular carcinomas was further observed. Moreover, elevation of CK8/18 was strongly associated with induction of cell proliferation in GST-P positive foci and tumors. In conclusion, our data imply that CK8/18 overexpression, those two cytokeratins complex formation associated with histone type 2 H2aa3 up-regulation and intermediate filament reorganization may drive neoplastic transformation of GST-P positive foci during rat hepatocarcinogenesis leading to the formation of hepatocellular carcinomas.
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