Senescence-associated gene YPEL3 is downregulated in human colon tumors

Rebecca Tuttle, Margo Simon, David C. Hitch, J. Nicholas Maiorano, Minia Hellan, James Ouellette, Paula Termuhlen, Steven J. Berberich

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8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1791-1796
Number of pages6
JournalAnnals of Surgical Oncology
Volume18
Issue number6
DOIs
StatePublished - Jun 2011

Bibliographical note

Funding Information:
ACKNOWLEDGMENT We acknowledge Dr. Jonathan Saxe, Dr. Kenneth Rundell, Dr. Damien Lebamoff, Dr. Phillip Williams, Dr. Dan Hood, Dr. Edward Ewing, and Dr. Richard Pelstring for their assistance with the collection of colon specimens. These studies were supported by the National Cancer Institute (CA66430 to S.J.B.).

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