67 263

Cited 0 times in

Spectrum of molecular changes during hepatocarcinogenesis induced by DEN and other chemicals in Fisher 344 male rats [Mechanisms of Ageing and Development 123 (2002) 1665-1680].

Authors
Lim, IK
Citation
Mechanisms of ageing and development, 124(5):697-708, 2003
Journal Title
Mechanisms of ageing and development
ISSN
0047-63741872-6216
Abstract
Unlike other tissues such as breast, colon and renal cell carcinoma, it is not an easy task to single out any representative oncogene or tumor suppressor genes in the development of hepatocellular carcinoma (HCC), which play a pivotal role. To investigate putatively altered main pathways in HCC, F344 male rats were treated with a single injection of N-nitrosodiethylamine (DEN), followed by either twice/week injections of nodularin for 10 weeks or thioacetamide (TAA) in drinking water for 39 weeks. p53 expression was dramatic in both hepatocytes and mesenchymal cells after a single injection of DEN, however, PCR-SSCP assay could not detect any p53 mutation during the development of hepatocellular adenoma (HCA). The data indicate that wtp53 response was mostly for removal of damaged cells during the initiation of carcinogenesis. When treated with DEN-TAA, induction of gankyrin expression during hepatic fibrosis preceded the loss of pRB protein, accompanied with significant expressions of G1phase cyclins and CDKs. Moreover, p16(INK4A) exon 1 was hypermethylated during the development of poorly differentiated HCCs. These changes would result in complete inactivation of the pRB regulatory pathway during hepatocarcinogenesis. Induction of TGF-beta1 expression with loss of its receptor expression occurred rapidly in the altered hepatocytes by DEN-nodularin treatment. CONCLUSION: Therefore, escape from TGF-beta1 induced apoptosis and severe degradation of pRB protein during the early stage of carcinogenesis can perform a symphony to proliferate and to transform the altered hepatocytes to tumor cells. Inactivation of p16(INK4A) and p53 genes at the later stage of carcinogenesis would endow HCC with malignancy, which is highly resistant to any therapeutic trials.
MeSH terms
Aging/physiology*Alkylating AgentsAnimalsCarcinoma, Hepatocellular/chemically inducedCarcinoma, Hepatocellular/geneticsCarcinoma, Hepatocellular/physiopathology*Cell Cycle/physiologyCyclin-Dependent Kinase Inhibitor p16/geneticsDNA DamageDiethylnitrosamineDisease Models, Animal*Liver Cirrhosis/pathologyLiver Cirrhosis/physiopathologyLiver Neoplasms/chemically inducedLiver Neoplasms/geneticsLiver Neoplasms/physiopathology*MalePeptides, CyclicRatsRats, Inbred F344*Retinoblastoma Protein/geneticsTransforming Growth Factor beta/geneticsTransforming Growth Factor beta1Tumor Suppressor Protein p53/genetics
PMID
12825548
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
임, 인경
Files in This Item:
Full-Text Not Available.txtDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse