Senescence-Associated Gene YPEL3 Is Downregulated in Human Colon Tumors

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

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Abstract

<p> <h3> Background </h3></p><p> 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 <em> YPEL3 </em> . <h3> Methods </h3></p><p> We collected colon tumor samples with matched normal control samples and analyzed them for <em> YPEL3 </em> gene expression by reverse transcriptase&ndash;polymerase chain reaction and CpG hypermethylation of the <em> YPEL3 </em> promoter by base-specific polymerase chain reaction analysis. Colon cancer cell lines (Caco-2 and HCT116&minus;/&minus; p53) were used to assess <em> YPEL3 </em> gene expression after treatment with 5-azadeoxycytidine or trichostatin A. <h3> Results </h3></p><p> Reverse transcriptase&ndash;polymerase chain reaction analysis demonstrated a decrease in <em> YPEL3 </em> expression in tumor samples when compared to their patient-matched normal tissue. We determined that DNA methylation of the <em> YPEL3 </em> promoter CpG island does not play a role in <em> YPEL3 </em> regulation in human colon tumors or colon cancer cells lines, consistent with the inability of 5-azadeoxycytidine treatment to induce <em> YPEL3 </em> expression in colon cancer cell lines. In contrast, colon cell line results suggest that histone acetylation may play a role in <em> YPEL3 </em> regulation in colon cancer. <h3> Conclusions </h3></p><p> <em> YPEL3 </em> is preferentially downregulated in human colon adenocarcinomas. DNA hypermethylation does not appear to be the mechanism of <em> YPEL3 </em> downregulation in this subset of collected patient samples or in colon cell lines. Histone acetylation may be a relevant epigenetic modulator of <em> YPEL3 </em> in colon adenocarcinomas. Future investigation of <em> YPEL3 </em> and its role in colon cancer signaling and development may lead to increased understanding and alternative treatment options for this disease.</p>
Original languageAmerican English
JournalAnnals of Surgical Oncology
Volume18
DOIs
StatePublished - Jun 1 2011

Keywords

  • Surgery
  • Surgical Oncology
  • Oncology

Disciplines

  • Medical Specialties
  • Medicine and Health Sciences
  • Oncology
  • Surgery

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