title: Calcium prevents tumorigenesis in a mouse model of colorectal cancer.
abstract: OBJECTIVE
  Calcium has been proposed as a mediator of the chemoprevention of colorectal cancer (CRC), but the comprehensive mechanism underlying this preventive effect is not yet clear. Hence, we conducted this study to evaluate the possible roles and mechanisms of calcium-mediated prevention of CRC induced by 1,2-dimethylhydrazine (DMH) in mice.
  
  
  METHODS
  For gene expression analysis, 6 non-tumor colorectal tissues of mice from the DMH + Calcium group and 3 samples each from the DMH and control groups were hybridized on a 4×44 K Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction (PCR). Functional analysis of the microarray data was performed using KEGG and Gene Ontology (GO) analyses. Hub genes were identified using Pathway Studio software.
  
  
  RESULTS
  The tumor incidence rates in the DMH and DMH + Calcium groups were 90% and 40%, respectively. Microarray gene expression analysis showed that S100a9, Defa20, Mmp10, Mmp7, Ptgs2, and Ang2 were among the most downregulated genes, whereas Per3, Tef, Rnf152, and Prdx6 were significantly upregulated in the DMH + Calcium group compared with the DMH group. Functional analysis showed that the Wnt, cell cycle, and arachidonic acid pathways were significantly downregulated in the DMH + Calcium group, and that the GO terms related to cell differentiation, cell cycle, proliferation, cell death, adhesion, and cell migration were significantly affected. Forkhead box M1 (FoxM1) and nuclear factor kappa-B (NF-κB) were considered as potent hub genes.
  
  
  CONCLUSIONS
  In the DMH-induced CRC mouse model, comprehensive mechanisms were involved with complex gene expression alterations encompassing many altered pathways and GO terms. However, how calcium regulates these events remains to be studied.
authors.affiliation: Division of Gastroenterology, Shanghai Jiao-Tong University School of Medicine, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Ji-Lin
authors.initials: JL
authors.lastname: Wang
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Lin
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Chen
authors.forename: Xuan
authors.initials: X
authors.lastname: Kong
authors.forename: Hua
authors.initials: H
authors.lastname: Xiong
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D019813:1,2-Dimethylhydrazine; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D040502:Calgranulin B / Q000235:genetics; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks; D053506:Matrix Metalloproteinase 10 / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D056950:Period Circadian Proteins / Q000235:genetics; D054465:Peroxiredoxin VI / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012259:Ribonuclease, Pancreatic / Q000235:genetics
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D040502:Calgranulin B; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; D016328:NF-kappa B; C512645:Per3 protein, mouse; D056950:Period Circadian Proteins; C489491:Tef protein, mouse; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse; C099439:Ang2 protein, mouse; D012259:Ribonuclease, Pancreatic; D053506:Matrix Metalloproteinase 10; D019813:1,2-Dimethylhydrazine; D002118:Calcium