Senescence-associated gene YPEL3 is downregulated in human colon tumors. Ann Surg Oncol 2011 Jun;18(6):1791-6
Date
01/27/2011Pubmed ID
21267786DOI
10.1245/s10434-011-1558-xScopus ID
2-s2.0-79956216777 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
BACKGROUND: Previous work has demonstrated YPEL3 to be a growth-suppressive protein that acts through a pathway of cellular senescence. We set out to determine whether human colon tumors demonstrated downregulation of YPEL3.
METHODS: We collected colon tumor samples with matched normal control samples and analyzed them for YPEL3 gene expression by reverse transcriptase-polymerase chain reaction and CpG hypermethylation of the YPEL3 promoter by base-specific polymerase chain reaction analysis. Colon cancer cell lines (Caco-2 and HCT116(-/-) p53) were used to assess YPEL3 gene expression after treatment with 5-azadeoxycytidine or trichostatin A.
RESULTS: Reverse transcriptase-polymerase chain reaction analysis demonstrated a decrease in YPEL3 expression in tumor samples when compared to their patient-matched normal tissue. We determined that DNA methylation of the YPEL3 promoter CpG island does not play a role in YPEL3 regulation in human colon tumors or colon cancer cells lines, consistent with the inability of 5-azadeoxycytidine treatment to induce YPEL3 expression in colon cancer cell lines. In contrast, colon cell line results suggest that histone acetylation may play a role in YPEL3 regulation in colon cancer.
CONCLUSIONS: YPEL3 is preferentially downregulated in human colon adenocarcinomas. DNA hypermethylation does not appear to be the mechanism of YPEL3 downregulation in this subset of collected patient samples or in colon cell lines. Histone acetylation may be a relevant epigenetic modulator of YPEL3 in colon adenocarcinomas. Future investigation of YPEL3 and its role in colon cancer signaling and development may lead to increased understanding and alternative treatment options for this disease.
Author List
Tuttle R, Simon M, Hitch DC, Maiorano JN, Hellan M, Ouellette J, Termuhlen P, Berberich SJMESH terms used to index this publication - Major topics in bold
AdenocarcinomaAdenocarcinoma, Mucinous
Adult
Aged
Aged, 80 and over
Carcinoma, Signet Ring Cell
Case-Control Studies
Cellular Senescence
Colon
Colonic Neoplasms
CpG Islands
DNA Methylation
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Signal Transduction
Tumor Cells, Cultured
Tumor Suppressor Proteins