SCTR regulates cell cycle-related genes toward anti-proliferation in normal breast cells while having pro-proliferation activity in breast cancer cells

Seongeun Kang, Byungtak Kim, Han Sung Kang, Gookjoo Jeong, Hansol Bae, Hyunkyung Lee, Seungyeon Lee, Sun Jung Kim

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Secretin receptor (SCTR), the G-protein coupled receptor (GPCR) for secretin, has been observed to be upregulated in a few tumor types while downregulated in others, promoting or suppressing the proliferation of tumor cells, respectively. However, little is known about the molecular regulatory mechanism of dysregulation in cancer. In the present study, an analysis of the biological pathways affected by methylation in breast cancer using the methylome databases revealed that GPCRs played a major part in the affected pathway. SCTR, one of the dysregulated GPCRs, showed hypermethylation (p<0.01) and downregulation (p<0.05) in breast cancer tissues. Pathway analysis after the downregulation of SCTR by siRNA in MCF-10A cells identified the G2/M stage checkpoint as the top-scored pathway. Cell cycle-related genes were all upregulated or downregulated suppressing cell proliferation. However, the overexpression of SCTR in MCF-7 cells led to a 35% increase of the cell proliferation index and 2.1-fold increase of cellular migration. Our findings indicate that SCTR suppresses the proliferation of normal breast cells, while the gene stimulates the proliferation and migration of cancer cells being downregulated by promoter methylation.

Original languageEnglish
Pages (from-to)1923-1931
Number of pages9
JournalInternational Journal of Oncology
Volume47
Issue number5
DOIs
StatePublished - 1 Nov 2015

Keywords

  • Breast cancer
  • Cell cycle
  • CpG methylation
  • G-protein coupled receptor
  • Network analysis
  • Secretin receptor

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