title: SCTR regulates cell cycle-related genes toward anti-proliferation in normal breast cells while having pro-proliferation activity in breast cancer cells.
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.
authors.affiliation: Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
authors.forename: Seongeun
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
authors.forename: Byungtak
authors.initials: B
authors.lastname: Kim
authors.affiliation: Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Han-Sung
authors.initials: HS
authors.lastname: Kang
authors.affiliation: Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
authors.forename: Gookjoo
authors.initials: G
authors.lastname: Jeong
authors.affiliation: Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
authors.forename: Hansol
authors.initials: H
authors.lastname: Bae
authors.affiliation: Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
authors.forename: Hyunkyung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
authors.forename: Seungyeon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D049109:Cell Proliferation / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor