title: c-Jun NH2-teminal kinase 1 interacts with vitamin D receptor and affects vitamin D-mediated inhibition of cancer cell proliferation.
abstract: Vitamin D is a chemopreventive agent that acts against colorectal carcinogenesis in vivo and in vitro through vitamin D receptor (VDR). Previous studies showed that stress-activated protein kinase JNKs (c-Jun NH2-terminal kinases) and p38 cooperated to activate VDR and increase vitamin D3-dependent growth inhibition in breast cancer cells. This study is to determine whether vitamin D-mediated inhibition of cell proliferation is associated with JNK1 in colorectal cancer cells.
  
  
  
  Human colon cancer cells were treated with calcitriol, an active vitamin D3. The results showed that calcitriol significantly inhibited cell proliferation and caused cell cycle arrest in HT29 cells, which was associated with induction of phosphorylated JNK1 (p-JNK). The induction of VDR and p-JNK by calcitriol was also observed in Caco-2 cells. Furthermore, VDR expression was significantly downregulated in JNK1-/- mouse intestinal epithelial cells, and VDR reporter activity was reduced in JNK1-/- mouse embryonic fibroblasts (MEFs). However, increasing activated JNK1 upregulated VDR expression and transcriptional activity in vitro. Moreover, JNK1 co-localized with VDR in nuclei and cytoplasm and physically bound together. Reduced expression of JNK1 and VDR in HT29 and Caco-2 cells and JNK1 absence in JNK1-/- MEFs attenuated calcitriol-mediated inhibition of cell proliferation.
  
  
  
  JNK1 physically and functionally interacted with VDR and positively regulated VDR expression at transcriptional and translational levels, which influenced calcitriol-mediated inhibition of cancer cell proliferation.
authors.affiliation: School of Life Science, Liaoning University, Shenyang, Liaoning 110036, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Bi
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pohl
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Huali
authors.initials: H
authors.lastname: Dong
authors.affiliation: School of Life Science, Liaoning University, Shenyang, Liaoning 110036, China.
authors.forename: Xichun
authors.initials: X
authors.lastname: Xia
authors.affiliation: School of Life Science, Liaoning University, Shenyang, Liaoning 110036, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China; Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China; Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA. Electronic address: wyang06@uic.edu.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002117:Calcitriol / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D008156:Luciferases; D048055:Mitogen-Activated Protein Kinase 8; D002117:Calcitriol
keywords: Cancer; JNK1; Vitamin D receptor