CBCRA
Canadian Breast Cancer Research Alliance
ACRCS
Alliance canadienne pour la recherche sur le cancer du sein
:
Search:
Advanced Search

Retroviral delivery of connexin genes to human breast tumor cells inhibits in vivo tumor growth by a mechanism that is independent of significant gap junctional intercellular communication

Show full item record

Title: Retroviral delivery of connexin genes to human breast tumor cells inhibits in vivo tumor growth by a mechanism that is independent of significant gap junctional intercellular communication
Author: Qin, H.; Shao, Q.; Curtis, H.; Galipeau, J.; Belliveau, D. J.; Wang, T.; Alaoui-Jamali, M. A.; Laird, D. W.
Abstract: The mechanism by which gap junction proteins, connexins, act as potent tumor suppressors remains poorly understood. In this study human breast tumor cells were found to exhibit diverse gap junction phenotypes including (a) undetectable Cx43 and no intercellular communication (HBL100); (b) low levels of Cx43 and sparse intercellular communication (MDA-MB-231); and (c) significant levels of Cx43 and moderate intercellular communication (Hs578T). Although retroviral delivery of Cx43 and Cx26 cDNAs to MDA-MB-231 cells did not achieve an expected substantial rescue of intercellular communication, overexpression of connexin genes did result in a dramatic suppression of tumor growth when connexin-expressing MDA-MB-231 cells were implanted into the mammary fat pad of nude mice. Subsequent immunolocalization studies on xenograph sections revealed only cytoplasmic stores of Cx43 and no detectable gap junctions. Moreover, DNA array and Western blot analysis demonstrated that overexpression of Cx43 or Cx26 in MDA-MB-231 cells down-regulated fibroblast growth factor receptor-3. Surprisingly, these results suggest that Cx43 and Cx26 induce their tumor-suppressing properties by a mechanism that is independent of significant gap junctional intercellular communication and possibly through the down-regulation of key genes involved in tumor growth. Moreover, our studies show that retroviruses are effective vehicles for delivering connexins to human breast tumor cells, facilitating potential gene therapy applications.
Description: This article is hosted on a website external to the CBCRA Open Access Archive. Selecting “View/Open” below will launch the full-text article in another browser window.
Publisher: American Society for Biochemistry and Molecular Biology
URI: http://hdl.handle.net/1807.1/168
Date: 2002-08

Files in this item

Files Size Description Format View
Quin.2002.29132.html 415bytes External link HTML View/Open

This item appears in the following category

Show full item record

Browse

Tools