Gene Set: WANG_HCP_PROSTATE_CANCER

Standard name WANG_HCP_PROSTATE_CANCER
Systematic name M17044
Brief description Genes with the high-CpG-density promoters (HCP) that were up-regulated in 1542-CP3TX cells (prostate cancer) compared to 1542-NPTX (normal prostate).
Full description or abstract Oligoarray analysis of a matched pair of prostate cancer and normal cell lines derived from the same radical prostatectomy specimen identified 113 candidate hypomethylated genes that were overexpressed in the cancer cells and contained CpG islands. Hypomethylation of wingless-related MMTV integration site 5A (WNT5A), S100 calcium-binding protein P (S100P) and cysteine-rich protein 1(CRIP1) was confirmed in the cancer cells by bisulfite sequencing. Treatment of the corresponding normal prostate epithelial cells 1542-NPTX with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-aza-CdR) induced higher levels of mRNA expression and partial loss of methylation on these genes. Primary prostate cancers were tested using methylation-specific polymerase chain reaction. WNT5A was hypomethylated in 11/17 (65%) tumors, S100P in 8/16 (50%) and CRIP1 in 13/20 (65%). Bisulfite sequencing of a section of the 5' untranslated region (UTR) of WNT5A revealed that three CpG sites (15, 24 and 35) were consistently methylated (93%) in the normal cell line and normal tissues, but not in the prostate cancer cell line and eight primary prostate cancers. Multiple putative binding sites for the transcription factors SP1 and AP-2 were found adjacent to CpG sites 15 and 24. A putative c-Myb binding site was located within the CpG site 35. Anti-c-Myb antibody co-precipitation with WNT5A was methylation-sensitive in 1542-NPTX cells. It is likely that an epigenetic mechanism regulates WNT5A expression in prostate cancer.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17486081   Authors: Wang Q,Williamson M,Bott S,Brookman-Amissah N,Freeman A,Nariculam J,Hubank MJ,Ahmed A,Masters JR
Exact source Table 1S
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform HUMAN_SEQ_ACCESSION
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Version history 3.0: First introduced

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