The Relationship Between DNA Methylation in Key Region and the Differential Expressions of Genes in Human Breast Tumor Tissue
DNA AND CELL BIOLOGY
Authors: Jin, Wen; Li, Qian-Zhong; Zuo, Yong-Chun; Cao, Yan-Ni; Zhang, Lu-Qiang; Hou, Rui; Su, Wen-Xia
Abstract
Breast cancer has a high mortality rate for females. Aberrant DNA methylation plays a crucial role in the occurrence and progression of breast carcinoma. By comparing DNA methylation differences between tumor breast tissue and normal breast tissue, we calculate and analyze the distributions of the hyper- and hypomethylation sites in different function regions. Results indicate that enhancer regions are often hypomethylated in breast cancer. CpG islands (CGIs) are mainly hypermethylated, while the flanking CGI (shores and shelves) is more easily hypomethylated. The hypomethylation in gene body region is related to the upregulation of gene expression, and the hypomethylation of enhancer regions is closely associated with gene expression upregulation in breast cancer. Some key hypomethylation sites in enhancer regions and key hypermethylation sites in CGIs for regulating key genes are, respectively, found, such as oncogenes ESR1 and ERBB2 and tumor suppressor genes FBLN2, CEBPA, and FAT4. This suggests that the recognizing methylation status of these genes will be useful for the diagnosis of breast cancer.
Anti-angiogenic and tumor-suppressive roles of candidate tumor-suppressor gene, Fibulin-2, in nasopharyngeal carcinoma
ONCOGENE
Authors: Law, E. W. L.; Cheung, A. K. L.; Kashuba, V. I.; Pavlova, T. V.; Zabarovsky, E. R.; Lung, H. L.; Cheng, Y.; Chua, D.; Kwong, D. Lai-wan; Tsao, S. W.; Sasaki, T.; Stanbridge, E. J.; Lung, M. L.
Abstract
Fibulin-2 (FBLN2) has been identified as a candidate tumor-suppressor gene in nasopharyngeal carcinoma (NPC). Originally identified through a chromosome 3 NotI genomic microarray screen, it shows frequent deletion or methylation in NPC. FBLN2 is located on chromosome 3p25.1 and is associated with tumor development through its important interactions with the extracellular matrix (ECM) proteins. FBLN2 encodes two isoforms. The short isoform (FBLN2S) is expressed abundantly in normal tissues, but is dramatically downregulated in NPC, while the long isoform (FBLN2L) is either not detectable or is expressed only at low levels in both normal and tumor tissues. Reintroduction of this FBLN2S inhibited cell proliferation, migration, invasion and angiogenesis in vitro. Furthermore, in vivo studies in nude mice show its expression is associated with tumor and angiogenesis suppression. FBLN2-associated angiogenesis occurs via concomitant downregulation of vascular endothelial growth factor and matrix metalloproteinase 2. This study provides compelling evidence that FBLN2S has an important tumor-suppressive and anti-angiogenic role in NPC. Oncogene (2012) 31, 728-738; doi:10.1038/onc.2011.272; published online 11 July 2011