The reduction of cell death and proliferation by p27(Kip1) minimizes DNA damage in an experimental model of genotoxicity.

Full Abstract

Hepatocellular carcinoma (HCC) is the fifth most commonly occurring cancer worldwide. The expression of p27 has been related to reduced severity of tumor grade and recurrence of HCC. The study assessed the role of p27 on the cell proliferation and death, and DNA mutagenesis in experimental genotoxicity induced by aflatoxin B1 (AFB(1)) in cultured hepatocytes obtained from control and p27(Kip1) deficient mice. The overexpression of p27 was assessed with wild type p27(Kip1) expression vector in HepG2 cells. The expression of p27, p21 and p53 was assessed in well and poorly-differentiated liver tumors. DNA damage and cell death induced by AFB(1) were related to a reduction of p27 and p21 expression in cultured hepatocytes. AFB(1)-induced nuclear phosphorylated (Ser 10) p27 degradation was related to a rise of nuclear KIST, Rsk-1 and Rsk-2 expression and cytoplasm phosphorylated (Thr 198) p27 expression. The overexpression of p27 reduced cell proliferation, cell death and DNA damage in AFB(1)-treated hepatocytes. The enhanced survival of patients with well differentiated compared to poorly-differentiated tumors was related to high expression of p27, p21 and p53 in liver sections. The study showed that the p27 reduced cell proliferation and death, as well as the accumulation of DNA damage in hepatocarcinogenesis.

Author information

Author/s: Ranchal, Isidora (I); González, Raúl (R); Bello, Rosario I (RI); Ferrín, Gustavo (G); Hidalgo, Ana B (AB); Linares, Clara I (CI); Aguilar-Melero, Patricia (P); González-Rubio, Sandra (S); Barrera, Pilar (P); Marchal, Trinidad (T); Nakayama, Keiichi I (KI); de la Mata, Manuel (M); Muntané, Jordi (J);

Affiliation: Liver Research Unit, Reina Sofia University Hospital, Córdoba, Spain.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 10) : pp 2270-80

Dates: Created 2009/09/28; Completed 2009/11/05;

PMID: 19672859, status: MEDLINE (last retrieval date: 11/5/2009, IMS Date: )

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aflatoxin B1 - toxicity
Animals
Apoptosis
Blotting, Western
Carcinoma, Hepatocellular - etiology; metabolism; pathology
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21 - genetics; metabolism
Cyclin-Dependent Kinase Inhibitor p27 - physiology
DNA Damage
Disease Models, Animal
Hepatocytes - cytology; drug effects; metabolism
Humans
Immunoenzyme Techniques

Associated Chemicals: Cyclin-Dependent Kinase Inhibitor p21 (0) ; Intracellular Signaling Peptides and Proteins (0) ; RNA, Messenger (0) ; Tumor Suppressor Protein p53 (0) ; Aflatoxin B1 (1162-65-8) ; Cyclin-Dependent Kinase Inhibitor p27 (147604-94-2) ; Ribosomal Protein S6 Kinases, 90-kDa (EC 2.7.1.37) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; RPS6KA1 protein, human (EC 2.7.11.1) ; UHMK1 protein, human (EC 2.7.11.1) ; ribosomal protein S6 kinase, 90kDa, polypeptide 3 (EC 2.7.11.1)

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