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Connexins and Gap Junctions in Mammary Gland Development and Breast Cancer Progression

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Abstract

The development and function of the mammary gland require precise control of gap junctional intercellular communication (GJIC). Here, we review the expression and function of gap junction proteins, connexins, in the normal mouse and human mammary gland. We then discuss the possible tumor-suppressive role of Cx26 and Cx43 in primary breast tumors and through the various stages of breast cancer metastasis and consider whether connexins or GJIC may actually promote tumorigenesis at some stages. Finally, we present in vitro data on the impact of connexin expression on breast cancer cell metastasis to the bone. We observed that Cx43 expression inhibited the invasive and migratory potentials of MDA-MB-231 breast cancer cells in a bone microenvironment, provided by the MC3T3-E1 mouse osteoblastic cell line. Expression of either Cx26 or Cx43 had no effect on MDA-MB-231 growth and adhesion under the influence of osteoblasts and did not result in regulation of osteogenic gene expression in these breast cancer cells. Furthermore, connexin-expressing MDA-MB-231 cells did not have an effect on the growth or differentiation of MC3T3-E1 cells. In summary, we conclude that connexin expression and GJIC are integral to the development and differentiation of the mammary gland. In breast cancer, connexins generally act as tumor suppressors in the primary tumor; however, in advanced breast tumors, connexins appear to act as both context-dependent tumor suppressors and facilitators of disease progression.

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Acknowledgment

We thank Isabelle Plant for providing the image for Figure 2 and Crystal Lounsbury for generating the artwork presented in Figures 1 and 4. This study was funded by the Canadian Institutes of Health Research and the Canadian Breast Cancer Research Alliance. E. M. holds a Terry Fox Foundation Studentship through the National Cancer Institute of Canada.

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  1. Department of Anatomy and Cell Biology, University of Western Ontario, London, N6A 5C1, Ontario, Canada

    Elizabeth McLachlan, Qing Shao & Dale W. Laird

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  1. Elizabeth McLachlan
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  2. Qing Shao
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Correspondence to Dale W. Laird.

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McLachlan, E., Shao, Q. & Laird, D.W. Connexins and Gap Junctions in Mammary Gland Development and Breast Cancer Progression. J Membrane Biol 218, 107–121 (2007). https://doi.org/10.1007/s00232-007-9052-x

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