ErbB-beta-catenin complexes are associated with human infiltrating ductal breast and murine mammary tumor virus (MMTV)-Wnt-1 and MMTV-c-Neu transgenic carcinomas.
Simultaneous deregulation of both Wnt and ErbB growth factors has previously been shown to result in the cooperative induction of mammary gland tumors. Using the murine mammary tumor virus (MMTV)-Wnt-1 transgenic model of mammary carcinoma, we have identified an unvarying association between beta-catenin and epidermal growth factor receptor/c-Neu (ErbB1/ErbB2) heterodimers in mammary gland tumors, indicating a requirement for ErbB signaling in Wnt-mediated tumorigenesis. Expansion of these observations to a second transgenic model, MMTV-c-Neu, demonstrated similar tumor-specific interactions, including an ErbB1 ligand-inducible phosphorylation of both beta-catenin and c-Neu. Direct relevance of these findings to human breast cancer was established upon examination of a set of human infiltrating ductal breast adenocarcinoma and lymph node metastasis tissues taken at surgery. These data revealed increased levels of beta-catenin in tumors and metastases versus normal breast as well as an association between beta-catenin and c-Neu that measurably occurs only in neoplasia, most strongly in metastatic lesions. These studies have identified a seemingly indispensable interaction between beta-catenin and epidermal growth factor receptor/c-Neu heterodimers in Wnt-1-mediated breast tumorigenesis that may indicate a fundamental signaling event in human metastatic progression.
Schroeder
Joyce A
JA
Tumor Biology Program and Department of Biochemistry and Molecular Biology, Mayo Medical/Graduate School, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259, USA.
Adriance
Melissa C
MC
McConnell
Elizabeth J
EJ
Thompson
Melissa C
MC
Pockaj
Barbara
B
Gendler
Sandra J
SJ
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008024:Ligands; D008324:Mammary Tumor Virus, Mouse / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D066246:ErbB Receptors; D008024:Ligands; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D014443:Tyrosine; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C495247:WNT1 protein, human; C495246:Wnt1 protein, mouse