Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer

doi:10.1016/j.bbrc.2003.12.079

Biochemical and Biophysical Research Communications

Volume 314, Issue 1, 30 January 2004, Pages 223-228

https://doi.org/10.1016/j.bbrc.2003.12.079 Get rights and content

Abstract

RUNX family transcription factors are integral components of TGF-β signaling pathways and have been implicated in cell cycle regulation, differentiation, apoptosis, and malignant transformation. It was noted previously that allele loss and loss of expression of RUNX3 are causally involved in gastric carcinogenesis. Our results demonstrate that RUNX3 is inactivated by aberrant DNA methylation in approximately 19% of lung cancer cell lines and 24% of primary lung cancer specimens. RUNX3 methylation is tumor-specific, since it is not observed in surrounding normal lung tissues. Our results suggest that loss of RUNX3 expression by DNA hypermethylation is frequently associated with the evolution of lung cancer.

Section snippets

Materials and methods

Cell lines and tissue samples. The human lung cancer cell lines NCI-H522, 86-2, A549, LK79, LK87, LCSC#1, LCSC#2, NCI-H23, NCI-H226, NCI-H460, NCI-H322, Sq-19, NCI-H1915, HS888 Lu, LX-1, Sq-1, Lu61, S2, Lu99, O2, SHP-77, QG-56, NCI-H125, Lu1 16, A-427, Calu-1, Calu-3, Calu-6, ChaGo-K-1, DMS114, and MRC9, and the human gastric cancer cell lines SUN16 and MKN28, were obtained from the Genetic Resources Center, Korea Research Institute of Bioscience and Biotechnology (GRC KRIBB, Taejeon, South

Frequent loss of RUNX3 expression in lung cancer

We examined the expression of RUNX3 in lung cancer cell lines by the reverse transcriptase-polymerase chain reaction (RT-PCR). As shown in Fig. 1, the expression of RUNX3 was undetectable in NCI-H226, NCI-H460, Sq-1, SHP-77, Calu-3, and Calu-6 cell lines, while control reaction products (GAPDH) were detected in all cell lines. Amplifications with two independent PCR primer sets yielded essentially the same results. Overall, of the 31 cell lines tested, 6 (19%) did not express RUNX3 at

Discussion

DNA methylation is a powerful mechanism for suppression of gene activity. The reciprocal relationship between the density of methylated cytosine residues in CpG islands and local transcriptional activity has been widely documented [12]. Transcriptional repression by DNA methylation is mediated by changes in chromatin structure. Specific proteins bound to methylated DNA recruit a complex containing transcriptional co-repressors and histone deacetylases [13]. The deacetylation of histones results

Acknowledgements

This work was supported by Korea Research Foundation Grant (KRF-2002-042-C00062) and the Creative Research Program (M10301000012) of the Ministry of Science and Technology of Korea to S.C. Bae.

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Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer

Abstract

Section snippets

Materials and methods

Frequent loss of RUNX3 expression in lung cancer

Discussion

Acknowledgements

Cancer Cell

Cell

Gene

Cell

Gene

Cancer Genet. Cytogenet.

Cell

J. Biol. Chem.

Curr. Opin. Genet. Dev.

Frequent allelic imbalance suggests involvement of a tumor suppressor gene at 1p36 in the pathogenesis of human lung cancers

Genes Chromosomes Cancer