RGD Reference Report - Expression of G1 cell cycle regulators in rat liver upon repeated exposure to thioacetamide. - Rat Genome Database

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Expression of G1 cell cycle regulators in rat liver upon repeated exposure to thioacetamide.

Authors: Kim, KT  Han, SY  Jeong, JS 
Citation: Kim KT, etal., Korean J Hepatol. 2007 Mar;13(1):81-90.
RGD ID: 2289136
Pubmed: PMID:17380078   (View Abstract at PubMed)

BACKGROUND AND AIMS: Eukaryotic cell cycle is regulated by signal transduction pathways mediated by complexes of cyclin dependent kinases (CDKs) and their partner cyclins, or by interaction with CDK inhibitors. Thioacetamide (TA) is a weak hepatocarcinogen causing several types of liver damage in a dose dependent manner and ultimately producing malignant transformation. We investigated alterations of expression of cell cycle regulators in the rat liver, involved in G1 entry and progression during TA administration. METHODS: We studied expression patterns of cyclin D1, CDK4, CDK6, p21(CIP1) and p16(INK4a) during daily intraperitoneal injection of low dose TA (50 mg/kg) till 7 day. We used western blot and immunohistochemistry for detection. RESULTS: Expression of cyclin D1, CDK4, CDK6 and p21(CIP1) increased from 6 hour and peaked at 2, 3 day, then decreased next 2 days, and re-increased at 6 day. Cytoplasmo-nuclear translocation of cyclin D1 and p21(CIP1) was evident within 1 day and prominent at 2 and 7 day. Expression of p16(INK4a) increased immediately after TA treatment and remarkably increased from 3 day and progressed till 7 day, showing cytoplasmic location, suggestive of inactive form. Most of in situ immunoreactions occurred at the centrilobular hepatocytes. Concomitant nuclear translocation of p21(CIP1) and cyclin D1, different with p16(INK4a) suggests that p21(CIP1) might be a transporter for nuclear translocation rather than cell cycle inhibitor. CONCLUSIONS: Daily administration of low dose TA makes cell cycle open and G1 progress, possibly due to cyclin D1, CDK4 and CDK 6, their transporter p21(CIP1), and inactive p16(INK4a), which occur at quiescent hepatocytes, not stem cells.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to organonitrogen compound  IDA 2289136 RGD 
response to organonitrogen compound  IEP 2289136 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccnd1  (cyclin D1)
Cdkn1a  (cyclin-dependent kinase inhibitor 1A)


Additional Information