Expressing connexin 43 in breast cancer cells reduces their metastasis to lungs.
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((R)). 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.
Li
Zhongyong
Z
Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Zhou
Zhiyi
Z
Welch
Danny R
DR
Donahue
Henry J
HJ
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement / Q000502:physiology; D018031:Connexin 43 / Q000235:genetics*; D017630:Connexins / Q000235:genetics; D017629:Gap Junctions / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000097002:Gap Junction beta-1 Protein
D053148:Caspase 3; D018031:Connexin 43; D017630:Connexins; D012333:RNA, Messenger; D000097002:Gap Junction beta-1 Protein