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

Isidora Ranchal, Raúl González, Rosario I. Bello, Gustavo Ferrín, Ana B. Hidalgo, Clara I. Linares, Patricia Aguilar-Melero, Sandra González-Rubio, Pilar Barrera, Trinidad Marchal, Keiichi I. Nakayama, Manuel De La Mata, Jordi Muntané

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2270-2280
Number of pages11
JournalInternational Journal of Cancer
Issue number10
Publication statusPublished - Nov 15 2009

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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