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Molecular and Cellular Biology, April 2006, p. 2976-2983, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.2976-2983.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Suppression of Intestinal Neoplasia by Deletion of Dnmt3b

Haijiang Lin,^1, Yasuhiro Yamada,^1,, Suzanne Nguyen,^2, Heinz Linhart,¹ Laurie Jackson-Grusby,^1, Alexander Meissner,¹ Konstantinos Meletis,^1,¶ Grace Lo,¹ and Rudolf Jaenisch^1,2*

Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142,¹ Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139²

Received 26 October 2005/ Returned for modification 22 December 2005/ Accepted 11 January 2006

Aberrant gene silencing accompanied by DNA methylation is associated with neoplastic progression in many tumors that also show global loss of DNA methylation. Using conditional inactivation of de novo methyltransferase Dnmt3b in Apc^Min/+ mice, we demonstrate that the loss of Dnmt3b has no impact on microadenoma formation, which is considered the earliest stage of intestinal tumor formation. Nevertheless, we observed a significant decrease in the formation of macroscopic colonic adenomas. Interestingly, many large adenomas showed regions with Dnmt3b inactivation, indicating that Dnmt3b is required for initial outgrowth of macroscopic adenomas but is not required for their maintenance. These results support a role for Dnmt3b in the transition stage between microadenoma formation and macroscopic colonic tumor growth and further suggest that Dnmt3b, and by extension de novo methylation, is not required for maintaining tumor growth after this transition stage has occurred.

H.L., Y.Y., and S.N. contributed equally to this study.

Present address: Department of Tumor Pathology, Gifu University, Japan.

Present address: Department of Pathology, Harvard Medical School, Boston, MA 02115.

^¶ Present address: Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.

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