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Connexin26 Regulates the Expression of Angiogenesis-Related Genes in Human Breast Tumor Cells by Both GJIC-Dependent and -Independent Mechanisms.
- Source :
-
Cell Communication & Adhesion . Jul-Dec2003, Vol. 10 Issue 4-6, p387-393. 7p. 17 Black and White Photographs, 1 Chart, 2 Graphs. - Publication Year :
- 2003
-
Abstract
- We previously reported that over-expression of connexins in mammary tumor cells retarded tumor growth in vivo in the absence of appreciable gap junction formation, highlighting a possible connexin-linked, but gap junctional intercellular communication (GJIC)-independent mechanism. In the current study, we engineered GJIC-deficient MDA-MB-435 human breast tumor cells to express a chimeric Cx26 where the green fluorescent protein was fused to the amino-terminal of Cx26 (GFP-Cx26). Characterization of this chimeric protein revealed that GFP-Cx26 assembled into non-functional gap junction-like clusters that were impermeable to Lucifer Yellow. In contrast, expression of wild-type Cx26 or Cx26 tagged at the carboxy terminal with yellow fluorescent protein, efficiently rescued GJIC in these tumor cells. Interestingly, by screening 96 tumor-related genes, we observed that the expression of Cx26 or GFP-Cx26 in the tumor cells up-regulated both the transcription and the translation of thrombospondin-1 (TSP-1), an anti-angiogenic molecule. Affymetrix array analysis extended the list of Cx26 or GFP-Cx26 regulated genes by ten candidates including connective tissue growth factor (CTGF), another angiogenesis-related gene. CTGF mRNA and protein levels were found to be down-regulated by both Cx26 and GFP-Cx26. Thus, our data indicates that Cx26 regulates angiogenesis-related molecules by mechanisms that are both GJIC-dependent and -independent. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15419061
- Volume :
- 10
- Issue :
- 4-6
- Database :
- Academic Search Index
- Journal :
- Cell Communication & Adhesion
- Publication Type :
- Academic Journal
- Accession number :
- 11715319
- Full Text :
- https://doi.org/10.1080/cac.10.4-6.387.393