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Epigenetic and genetic alterations of PTEN in hepatocellular carcinoma
Author(s) -
Wang Li,
Wang WenLiang,
Zhang Yong,
Guo ShuangPing,
Zhang Jing,
Li QinLong
Publication year - 2007
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2007.00042.x
Subject(s) - pten , tensin , epigenetics , biology , cancer research , carcinogenesis , dna methylation , methylation , hepatocellular carcinoma , microbiology and biotechnology , gene , gene expression , genetics , pi3k/akt/mtor pathway , apoptosis
Aim: To investigate the roles of epigenetic and genetic alterations of the phosphatase and tensin homologue on chromosome 10 gene (PTEN) in carcinogenesis and the development of hepatocellular carcinomas (HCC). Methods: A total of 56 cases of HCC tissues and six liver cell lines were studied for the expression of PTEN by immunohistochemistry and Western blot analysis. The PTEN gene mutations in exon5 and exon8 were detected by a combination of single‐strand conformation polymorphism (SSCP) analysis and DNA sequencing. Methylation‐specific PCR (MSP) was used to identify PTEN promoter methylation. Results: Of the 56 cases of HCC, 24 (42.9%) expressed the PTEN protein. All surrounding liver tissues of the hepatoma (32 cases) were positive for PTEN. Of the six cell lines, three liver cancer cell lines showed a low expression of PTEN. Five mutations of 56 HCC samples were detected. All of them were located at intron4. No mutation was found in exon5 and exon8. After MSP analysis, we found nine cases of PTEN promoter methylation in 56 specimens (16.1%). However, no CpG island of PTEN was found to be methylated in all six liver cell lines. Conclusion: The level of PTEN protein was altered in part of the HCC. The downregulation of PTEN expression may not be mainly associated with the PTEN mutations, but partly due to PTEN promoter methylation and other epigenetic regulation.