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

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((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.

journal_name

Clin Exp Metastasis

authors

Li Z,Zhou Z,Welch DR,Donahue HJ

doi

10.1007/s10585-008-9208-9

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

893-901

issue

8

eissn

0262-0898

issn

1573-7276

journal_volume

25

pub_type

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