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Expressing connexin 43 in breast cancer cells reduces their metastasis to lungs

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Abstract

Recently the concept that gap junctions play a role in cancer cell metastasis has emerged. However, the mechanism by which this might occur is unknown. To examine this issue a metastatic breast cancer cell line, MDA-MB-435, was stably transfected with human Cx43 cDNA. Four clones of 435 transfectants (435/Cx43+ c1, c6, c8, c14) and two clones of plasmid control (435/hy) were isolated and examined in this study. We found that expressing Cx43 in MDA-MB-435 cells decreased their expression of Cx32 but did not affect gap junctional intercellular communication, migration or invasion through Matrigel®. However, forced expression of Cx43 decreased the growth of MDA-MB-435 cells, decreased expression of N-cadherin, which is frequently associated with an aggressive phenotype, and increased MDA-MB-435 sensitivity to apoptosis. More importantly, there were fewer lung metastases in mice injected with 435/Cx43+ cells relative to mice injected with 435/hy. These results suggest that expressing Cx43 in breast cancer cells decreases their metastatic potential through a mechanism independent of gap junctional communication but, rather, related to N-cadherin expression and apoptosis.

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Abbreviations

GJIC:

Gap junctional intercellular communication

Cx:

Connexin

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Acknowledgements

This work was supported by the National Institute of Health grants CA90991 and AG13087 to Henry J. Donahue and CA87228 to Danny R. Welch.

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Authors and Affiliations

  1. Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Zhongyong Li, Zhiyi Zhou & Henry J. Donahue

  2. Departments of Pathology, Cell Biology and Pharmacology/Toxicology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA

    Danny R. Welch

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  1. Zhongyong Li
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  2. Zhiyi Zhou
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  3. Danny R. Welch
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  4. Henry J. Donahue
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Correspondence to Henry J. Donahue.

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Li, Z., Zhou, Z., Welch, D.R. et al. Expressing connexin 43 in breast cancer cells reduces their metastasis to lungs. Clin Exp Metastasis 25, 893–901 (2008). https://doi.org/10.1007/s10585-008-9208-9

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  • DOI: https://doi.org/10.1007/s10585-008-9208-9

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