%0 Journal Article
%T Wnt1 is epistatic to Id2 in inducing mammary hyperplasia, ductal side-branching, and tumors in the mouse
%A Susan Marino
%A Claire Romelfanger
%A Yoshifumi Yokota
%A Roel Nusse
%J BMC Cancer
%D 2004
%I BioMed Central
%R 10.1186/1471-2407-4-91
%X We have asked whether functional Id2 expression is necessary for Wnt induced mammary hyperplasia, side branching, and cancer, by generating mice expressing a Wnt1 transgene in an Id2 mutant background.We show in this work that forced expression of Wnt1 in the mammary gland is capable of overcoming the block to proliferation caused by the absence of Id2. We also show that Wnt1 expression is able to cause mammary tumors in an Id2 mutant background.We conclude that functional Id2 expression is not required for Wnt1 to induce mammary hyperplasia and mammary tumors.Basic helix-loop-helix (bHLH) transcription factors such as MyoD, E12, and E47 are key regulators of gene expression and control many differentiation events during development [1-3]. These transcription factors bind E-box or E-box-like sequences as homo-or heterodimers, and control the transcription of target genes containing these sequences in their promoters. The HLH domains dimerize with each other, whereas the basic domains bind to DNA. The Id (Inhibitor of DNA binding) proteins are HLH proteins that lack a basic domain. Id proteins act as dominant inhibitors of bHLH transcription factors by blocking their ability to bind to DNA and activate gene transcription [2,3]. Since the bHLH proteins regulate cell-type specific gene expression during cell commitment and differentiation, the formation of inactive heterodimers of bHLH proteins with Id proteins inhibits the commitment and differentiation the bHLH proteins promote.There are 4 mammalian Id genes, which show differences in their patterns of expression and function [2,3]. One of them, Id2, is expressed in glandular and ductal epithelium of the mouse mammary gland and has also been implicated in its development. Mammary glands of female mice that are homozygous mutant for Id2 have impaired lobulo-alveolar development [4]. In several tissues, including colon tumors induced by activation of the Wnt pathway, the expression of Id2 is regulated by Wnt-¦Â catenin
%U http://www.biomedcentral.com/1471-2407/4/91