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  • Oncogenomics
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Identification of genes differentially expressed in mouse mammary epithelium transformed by an activated β-catenin

Oncogene volume 22, pages 4594–4610 (2003)Cite this article

Abstract

β-Catenin is an executor of Wnt signaling and it can control cell fate and specification. Deletion of exon 3 from the endogenous β-catenin gene in differentiating mammary alveolar epithelium of the mouse results in the generation of an activated protein that lacks amino acids 5–80. This is accompanied by a loss of mammary epithelial differentiation and a transdifferentiation process to squamous metaplasias. To further understand the molecular process of transdifferentiation, the expression of genes in mammary tissue was profiled in the absence and presence of activated of β-catenin. Microarrays were generated that carry about 8500 cDNA clones with approximately 6000 obtained from mammary tissue. Mutant tissues, which had undergone either partial (TD1) or complete (TD2) squamous transdifferentiation, were compared with wild-type mammary tissue. Four groups of genes were identified. Group 1 contained genes whose expression was induced in both mutant tissues. Groups 2 and 3 contained genes that were active preferentially in TD2 and TD1, respectively. Group 4 contained genes suppressed in both samples. Using this approach, known and unknown genes activated in the transdifferentiation process were identified. A new 20 kDa protein (PANE1) induced upon transdifferentiation was nuclear in nonconfluent cells and cytoplasmic in confluent or dividing cells. Lastly, stabilization of β-catenin resulted in the retention of differentiated epithelium upon involution and altered activities of several proteases in transdifferentiated mammary epithelium.

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Acknowledgements

We thank Dr Makoto Mark Taketo for the floxed β-catenin mice and Dr John Hanover for the confocal verification of nuclear localization in the transfected samples. We also thank Gertraud Robinson for review of the manuscript, and the members of the Laboratory of Genetics and Physiology for essential discussions.

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Author notes

  1. Jean-Pierre Renou and Brian Bierie: Co-first author

Authors and Affiliations

  1. Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892, MD, USA

    Jean-Pierre Renou, Brian Bierie, Keiko Miyoshi, Yongzhi Cui & Lothar Hennighausen

  2. Institut National de la Recherche Agronomique, Jouy-en-Josas Cedex, France

    Jean-Pierre Renou & Jean Djiane

  3. Department of Biochemistry, School of Dentistry, The University of Tokushima, Tokushima, Japan

    Keiko Miyoshi

  4. Agricultural Research Organization, Volcani Center, Bet Dagan, Israel

    Moshe Reichenstein & Moshe Shani

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Correspondence to Lothar Hennighausen.

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Renou, JP., Bierie, B., Miyoshi, K. et al. Identification of genes differentially expressed in mouse mammary epithelium transformed by an activated β-catenin. Oncogene 22, 4594–4610 (2003). https://doi.org/10.1038/sj.onc.1206596

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