Connexins in Prostate Cancer Initiation and Progression
Annual rept. 1 Sep 2011-31 Aug 2012
NEBRASKA UNIV LINCOLN
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Gap junctions GJ are conglomerations of cell-cell channels that are formed by a family of 21 distinct proteins, called connexin Cxs. The Cxs transmembrane proteins and are designated according to molecular mass. They are assembled into GJs through many steps Figure 1. Communication through GJs is crucial for maintaining homeostasis 12. Impaired, or loss of, Cx expression has been documented in the pathogenesis of various carcinomas 13-5. Moreover, many studies have shown that over-expression of Cxs in tumor cells attenuates the malignant phenotype in vivo and in vitro, reverses the changes associated with epithelial to mesenchymal transformation EMT, and induces differentiation 346. For example, Cx32 is expressed in the liver, lung, and exocrine glands, and knock out studies have shown that the incidence of carcinogen induced tumors in these mice is higher 7-9. Moreover, mutations in several Cx genes have been characterized in inherited diseases associated with aberrant proliferation and differentiation 110. These studies support the notion that Cxs act as tumor suppressors. Despite this the molecular mechanisms by which GJs are assembled and disassembled are poorly understood.
- Anatomy and Physiology
- Medicine and Medical Research