title: Characterization of a beta-catenin nuclear localization defect in MCF-7 breast cancer cells.
abstract: Beta-catenin plays a key role in transducing Wnt signals from the plasma membrane to the nucleus. Here we characterize an unusual subcellular distribution of beta-catenin in MCF-7 breast cancer cells, wherein beta-catenin localizes to the cytoplasm and membrane but atypically did not relocate to the nucleus after Wnt treatment. The inability of Wnt or the Wnt agonist LiCl to induce nuclear localization of beta-catenin was not due to defective nuclear transport, as the transport machinery was intact and ectopic GFP-beta-catenin displayed rapid nuclear entry in living cells. The mislocalization is explained by a shift in the retention of beta-catenin from nucleus to cytoplasm. The reduced nuclear retention is caused by unusually low expression of lymphoid enhancer factor/T-cell factor (LEF/TCF) transcription factors. The reconstitution of LEF-1 or TCF4 expression rescued nuclear localization of beta-catenin in Wnt treated cells. In the cytoplasm, beta-catenin accumulated in recycling endosomes, golgi and beta-COP-positive coatomer complexes. The peripheral association with endosomes diminished after Wnt treatment, potentially releasing β-catenin into the cytoplasm for nuclear entry. We propose that in MCF-7 and perhaps other breast cancer cells, beta-catenin may contribute to cytoplasmic functions such as ER-golgi transport, in addition to its transactivation role in the nucleus.
authors: Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
authors: Cara
authors: C
authors: Jamieson
authors: Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
authors: Kate M
authors: KM
authors: Mills
authors: Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
authors: Christina
authors: C
authors: Lui
authors: Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia; Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.
authors: Crystal
authors: C
authors: Semaan
authors: Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.
authors: Mark P
authors: MP
authors: Molloy
authors: Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
authors: Manisha
authors: M
authors: Sharma
authors: School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
authors: Jade K
authors: JK
authors: Forwood
authors: Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia. Electronic address: beric.henderson@sydney.edu.au.
authors: Beric R
authors: BR
authors: Henderson
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D015533:Transcriptional Activation / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D004268:DNA-Binding Proteins; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Beta-catenin; Endosomes; Golgi; MCF-7 breast cancer cells; Nuclear localization; Wnt