title: The forkhead box M1 transcription factor contributes to the development and growth of mouse colorectal cancer.
abstract: OBJECTIVE
  In this study, we used Forkhead Box m1b (Foxm1b) transgenic mice and conditional Foxm1 knock-out mice to examine the role of Foxm1 in colon cancer development and proliferation.
  
  
  METHODS
  To induce mouse colorectal cancer, we used a single intraperitoneal injection of azoxymethane (AOM) followed by three 1-week cycles of 2.5% dextran sodium sulfate (DSS) water, each cycle separated by 2 weeks. For these colon tumor studies, we used either Rosa26-Foxm1b transgenic mice that ubiquitously expressed the human Foxm1b complementary DNA or mice in which the Foxm1 fl/fl targeted allele was deleted in colonic epithelial cells using the gut-specific Villin-Cre recombinase transgene (Villin-Cre). Colorectal tumor number and bromodeoxyuridine labeling were determined in Rosa26-Foxm1b mice, Villin-Cre Foxm1-/-, mice and wild-type mice after 12 weeks of AOM/DDS exposure. We also used Foxm1 small interfering RNA-depleted human DLD1 and mouse CT26 colon cancer cell lines to examine DNA replication and anchorage-independent growth.
  
  
  RESULTS
  After 12 weeks of treatment with AOM/DSS, Rosa26 Foxm1b transgenic mice showed an increase in the number and size of colorectal tumors compared with wild-type mice. Likewise, a significant reduction in the development and growth of colorectal tumors was found in Villin-Cre Foxm1-/- mice compared with Foxm1 fl/fl mice after AOM/DSS treatment, which was associated with decreased expression of cyclin A2, cyclin B1, survivin, and T-cell factor 4 genes. Moreover, Foxm1-depleted colon cancer cell lines showed reduced DNA replication and anchorage-independent growth.
  
  
  CONCLUSIONS
  These studies suggest that Foxm1 is critical for the proliferation and growth of colorectal cancer.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, USA. yyoshida@gh.med.osaka-u.ac.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Wang
authors.forename: Helena M
authors.initials: HM
authors.lastname: Yoder
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Davidson
authors.forename: Robert H
authors.initials: RH
authors.lastname: Costa
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic; D001397:Azoxymethane / Q000633:toxicity; D014408:Biomarkers, Tumor / Q000235:genetics; D001973:Bromodeoxyuridine; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019925:Cyclin A / Q000235:genetics; D056751:Cyclin A2; D019926:Cyclin B / Q000235:genetics; D056744:Cyclin B1; D016264:Dextran Sulfate / Q000633:toxicity; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D022661:RNA, Untranslated; D012097:Repressor Proteins; D000077022:Survivin; D051820:TCF Transcription Factors / Q000235:genetics; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D000964:Antimetabolites, Antineoplastic; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C117749:Birc5 protein, mouse; C503721:CCNA2 protein, human; C508184:CCNA2 protein, mouse; C534699:CCNB1 protein, human; D002273:Carcinogens; C534700:Ccnb1 protein, mouse; D019925:Cyclin A; D056751:Cyclin A2; D019926:Cyclin B; D056744:Cyclin B1; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D012097:Repressor Proteins; D000077022:Survivin; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; D016264:Dextran Sulfate; D001973:Bromodeoxyuridine; D001397:Azoxymethane