BACKGROUND/AIMS: The chromosome locus 3p21.3 is a "hot-spot" for chromosomal aberrations and loss of heterozygosity in cancers. The 35 genes mapped to the AP20 subregion of this locus were screened for their expression to identify candidate tumor suppressor genes. DLEC1 was selected for further characterization in primary hepatocellular carcinomas and cell lines. METHODS: RT-PCR and methylation-specific PCR were performed to examine the expression and methylation. Stable clones with DLEC1 overexpression were established to analyze cell proliferation and cell cycle. RESULTS: DLEC1 was silenced and hypermethylated in 9 of 11 cell lines examined. Treatment with 5-aza-2'-deoxycytidine reversed the methylation and restored DLEC1 expression. The correlation between hypermethylation and expression was also demonstrated in 10 pairs of hepatocellular carcinoma and adjacent normal tissues (t-test, p<0.05). Hypermethylation of DLEC1 was detected in 70.6% of tumors, compared to 10.3% in normal tissues (n=68, p<0.001, chi(2)). Of interest, DLEC1 methylation was associated with the AJCC staging of the tumors (p=0.036, chi(2)). DLEC1 over-expression in cell lines decreased colony formation, cell growth and cell size, and induced a G1 arrest in cell cycle. CONCLUSIONS: Our data indicate that DLEC1 is a candidate tumor suppressor gene that plays an important role in the development and progression of hepatocellular carcinoma.
BACKGROUND/AIMS: The chromosome locus 3p21.3 is a "hot-spot" for chromosomal aberrations and loss of heterozygosity in cancers. The 35 genes mapped to the AP20 subregion of this locus were screened for their expression to identify candidate tumor suppressor genes. DLEC1 was selected for further characterization in primary hepatocellular carcinomas and cell lines. METHODS: RT-PCR and methylation-specific PCR were performed to examine the expression and methylation. Stable clones with DLEC1 overexpression were established to analyze cell proliferation and cell cycle. RESULTS:DLEC1 was silenced and hypermethylated in 9 of 11 cell lines examined. Treatment with 5-aza-2'-deoxycytidine reversed the methylation and restored DLEC1 expression. The correlation between hypermethylation and expression was also demonstrated in 10 pairs of hepatocellular carcinoma and adjacent normal tissues (t-test, p<0.05). Hypermethylation of DLEC1 was detected in 70.6% of tumors, compared to 10.3% in normal tissues (n=68, p<0.001, chi(2)). Of interest, DLEC1 methylation was associated with the AJCC staging of the tumors (p=0.036, chi(2)). DLEC1 over-expression in cell lines decreased colony formation, cell growth and cell size, and induced a G1 arrest in cell cycle. CONCLUSIONS: Our data indicate that DLEC1 is a candidate tumor suppressor gene that plays an important role in the development and progression of hepatocellular carcinoma.
Authors: Lili Li; Jianming Ying; Xin Tong; Lan Zhong; Xianwei Su; Tingxiu Xiang; Xingsheng Shu; Rong Rong; Lei Xiong; Hongyu Li; Anthony T C Chan; Richard F Ambinder; Yajun Guo; Qian Tao Journal: Cell Mol Life Sci Date: 2013-10-25 Impact factor: 9.261
Authors: Brigette B Y Ma; Fion Sung; Qian Tao; Fan Fong Poon; Vivian W Lui; Winnie Yeo; Stephen L Chan; Anthony T C Chan Journal: Invest New Drugs Date: 2009-01-27 Impact factor: 3.850
Authors: Hye-Jung E Chun; Emilia L Lim; Alireza Heravi-Moussavi; Saeed Saberi; Karen L Mungall; Mikhail Bilenky; Annaick Carles; Kane Tse; Inna Shlafman; Kelsey Zhu; Jenny Q Qian; Diana L Palmquist; An He; William Long; Rodrigo Goya; Michelle Ng; Veronique G LeBlanc; Erin Pleasance; Nina Thiessen; Tina Wong; Eric Chuah; Yong-Jun Zhao; Jacquie E Schein; Daniela S Gerhard; Michael D Taylor; Andrew J Mungall; Richard A Moore; Yussanne Ma; Steven J M Jones; Elizabeth J Perlman; Martin Hirst; Marco A Marra Journal: Cancer Cell Date: 2016-03-14 Impact factor: 31.743
Authors: Christopher J Ricketts; Mark R Morris; Dean Gentle; Michael Brown; Naomi Wake; Emma R Woodward; Noel Clarke; Farida Latif; Eamonn R Maher Journal: Epigenetics Date: 2012-03 Impact factor: 4.528