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.
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.
Authors: Cullen M Taniguchi; Jonathon Winnay; Tatsuya Kondo; Roderick T Bronson; Alexander R Guimaraes; José O Alemán; Ji Luo; Gregory Stephanopoulos; Ralph Weissleder; Lewis C Cantley; C Ronald Kahn Journal: Cancer Res Date: 2010-06-08 Impact factor: 12.701
Authors: Mark J Hoenerhoff; Arun R Pandiri; Stephanie A Lahousse; Hu-Hua Hong; Tai-Vu Ton; Tiwanda Masinde; Scott S Auerbach; Kevin Gerrish; Pierre R Bushel; Keith R Shockley; Shyamal D Peddada; Robert C Sills Journal: Toxicol Pathol Date: 2011-05-13 Impact factor: 1.902
Authors: William H Chappell; Stephen L Abrams; Richard A Franklin; Michelle M LaHair; Giuseppe Montalto; Melchiorre Cervello; Alberto M Martelli; Ferdinando Nicoletti; Saverio Candido; Massimo Libra; Jerry Polesel; Renato Talamini; Michele Milella; Agostino Tafuri; Linda S Steelman; James A McCubrey Journal: Cell Cycle Date: 2012-11-16 Impact factor: 4.534