Wnt/beta-catenin and estrogen signaling converge in vivo.
Wnt and estrogen signaling represent important regulatory pathways, each controlling a wide range of biological processes. While an increasing number of observations suggest potential convergence between these pathways, no direct evidence of their functional interaction has been reported. Using human colon and breast cancer cells, we found that estrogen receptor (ER) alpha- and beta-catenin precipitated within the same immunocomplexes, reciprocally enhanced the transactivation of cognate reporter genes, and were reciprocally recruited to cognate response elements in the promoters of endogenous target genes. Using transgenic Drosophila that ectopically expressed human ERalpha alone or together with metabolically stable beta-catenin/Armadillo mutants, we demonstrated genetic interaction between these signal transducers in vivo. Thus, we present here the first direct evidence of cross-talk between Wnt and estrogen signaling pathways via functional interaction between beta-catenin and ERalpha.
The Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Alexander P
AP
Kouzmenko
Ken-Ichi
K
Takeyama
Saya
S
Ito
Takashi
T
Furutani
Shun
S
Sawatsubashi
Akio
A
Maki
Eriko
E
Suzuki
Yoshihiro
Y
Kawasaki
Tetsu
T
Akiyama
Testuya
T
Tabata
Shigeaki
S
Kato
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D009154:Mutation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D019076:Transgenes; D051176:beta Catenin
C495270:CTNNB1 protein, human; D002843:Chromatin; D003598:Cytoskeletal Proteins; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen; D015534:Trans-Activators; D051176:beta Catenin