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

Academic Article

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 MatrigelĀ®. 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. Ā© 2008 Springer Science+Business Media B.V.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Li Z; Zhou Z; Welch DR; Donahue HJ
  • Start Page

  • 893
  • End Page

  • 901
  • Volume

  • 25
  • Issue

  • 8