PLoS ONE (Jan 2015)

Promoter hypermethylation-related reduced somatostatin production promotes uncontrolled cell proliferation in colorectal cancer.

  • Katalin Leiszter,
  • Ferenc Sipos,
  • Orsolya Galamb,
  • Tibor Krenács,
  • Gábor Veres,
  • Barna Wichmann,
  • István Fűri,
  • Alexandra Kalmár,
  • Árpád V Patai,
  • Kinga Tóth,
  • Gábor Valcz,
  • Zsolt Tulassay,
  • Béla Molnár

DOI
https://doi.org/10.1371/journal.pone.0118332
Journal volume & issue
Vol. 10, no. 2
p. e0118332

Abstract

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BackgroundSomatostatin (SST) has anti-proliferative and pro-apoptotic effects. Our aims were to analyze and compare the SST expression during normal aging and colorectal carcinogenesis at mRNA and protein levels. Furthermore, we tested the methylation status of SST in biopsy samples, and the cell growth inhibitory effect of the SST analogue octreotide in human colorectal adenocarcinoma cell line.MethodsColonic samples were collected from healthy children (n1 = 6), healthy adults (n2 = 41) and colorectal cancer patients (CRCs) (n3 = 34) for SST mRNA expression analysis, using HGU133 Plus2.0 microarrays. Results were validated both on original (n1 = 6; n2 = 6; n3 = 6) and independent samples ((n1 = 6; n2 = 6; n3 = 6) by real-time PCR. SST expressing cells were detected by immunohistochemistry on colonic biopsy samples (n1 = 14; n2 = 20; n3 = 23). The effect of octreotide on cell growth was tested on Caco-2 cell line. SST methylation percentage in biopsy samples (n1 = 5; n2 = 5; n3 = 9) was defined using methylation-sensitive restriction enzyme digestion.ResultsIn case of normal aging SST mRNA expression did not alter, but decreased in cancer (p ConclusionsIn cancerous colonic mucosa the reduced SST production may contribute to the uncontrolled cell proliferation. Our observation that in colon cancer cells octreotide significantly enhanced cell death and attenuated cell proliferation suggests that SST may act as a regulator of epithelial cell kinetics. The inhibition of SST expression in CRC can be epigenetically regulated by promoter hypermethylation.