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Background & aims

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."xsd:string
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http://purl.uniprot.org/citations/17408638http://purl.uniprot.org/core/author"Costa R.H."xsd:string
http://purl.uniprot.org/citations/17408638http://purl.uniprot.org/core/author"Yoshida Y."xsd:string
http://purl.uniprot.org/citations/17408638http://purl.uniprot.org/core/author"Davidson N.O."xsd:string
http://purl.uniprot.org/citations/17408638http://purl.uniprot.org/core/author"Wang I.C."xsd:string
http://purl.uniprot.org/citations/17408638http://purl.uniprot.org/core/author"Yoder H.M."xsd:string
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http://purl.uniprot.org/citations/17408638http://purl.uniprot.org/core/name"Gastroenterology"xsd:string
http://purl.uniprot.org/citations/17408638http://purl.uniprot.org/core/pages"1420-1431"xsd:string
http://purl.uniprot.org/citations/17408638http://purl.uniprot.org/core/title"The forkhead box M1 transcription factor contributes to the development and growth of mouse colorectal cancer."xsd:string
http://purl.uniprot.org/citations/17408638http://purl.uniprot.org/core/volume"132"xsd:string
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