The connexins are a family of proteins that form the intercellular membrane channels of gap junctions. Genes encoding 13 different rodent connexins have been cloned and characterized to date. Connexins vary both in their distribution among adult cell types and in the properties of the channels that
Inducible expression of the gap junction protein connexin43 decreases the neoplastic potential of HT-1080 human fibrosarcoma cells in vitro and in vivo
✍ Scribed by Timothy J. King; Laurie H. Fukushima; Yutaka Yasui; Paul D. Lampe; John S. Bertram
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 264 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0899-1987
- DOI
- 10.1002/mc.10071
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✦ Synopsis
Abstract
Numerous studies have demonstrated a correlation between dysregulation/loss of connexin expression or gap junction intercellular communication (GJIC) function and decreased growth control both in human tumors and tumor cell lines. Likewise, restoration of constitutive connexin expression/function is correlated with increased growth control/decreased tumorigenicity. Here, we show for the first time that inducible restoration of connexin43 (Cx43) expression and GJIC function in a human tumor line of mesenchymal origin (HT‐1080, fibrosarcoma) resulted in a lowered neoplastic potential. Specifically, HT‐1080 cells induced to express Cx43 demonstrated diminished foci formation when in co‐culture with normal fibroblasts, decreased colony formation under anchorage‐independent conditions, and reduced tumor growth when injected into immunodeficient mice. These results, obtained utilizing an inducible system that helps address issues of clonal heterogeneity, strongly implicate Cx43 as a tumor suppressor in human tissue of mesenchymal origin and GJIC as a regulatory mechanism for cellular growth control both in vitro and in vivo. This study also further supports the hypothesis that loss of Cx43/GJIC in human tumors may play an important role in the dysregulation of normal growth control. © 2002 Wiley‐Liss, Inc.
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