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Abstract
Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressive properties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. To explore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80 cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent control tissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibody indicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as compared to the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed the down regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association (p<0.05) with the histological type and tumor invasion properties of the cancer. Our data demonstrated that loss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significant insights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for colon cancer.
Highlights
Connexins constitutes a family of structurally related transmembrane proteins that connect two adjacent cells by forming gap junctions (Sohl and Willecke, 2004)
Each gap junction is composed of two hemichannels, or connexons and each connexon is constituted of six connexin proteins
Connexin 43 (Cx43) is down-regulated in human colon cancer In order to explore the expression dynamics of tumor suppressor Cx43 protein in human colon tissue, we investigated its protein expression in the tumor samples and compared them with the adjacent normal tissue
Summary
Connexins constitutes a family of structurally related transmembrane proteins that connect two adjacent cells by forming gap junctions (Sohl and Willecke, 2004). Each gap junction is composed of two hemichannels, or connexons and each connexon is constituted of six connexin proteins. Connexins are multi-functional proteins with diverse role in the cell physiology. Connexins are known to regulate the embryonic development, apoptosis, differentiation, tissue homeostasis and metabolic transport (Dbouk et al, 2009). Cx43 is abundantly expressed in the human tissues, including the colon cells (Kanczuga-Koda et al, 2004). The carboxy-terminal (CT) region of the Cx43 acts as a regulatory domain that can interact with the cytoplasmic microenvironment and co-ordinate various functions of Cx43. Many functions of Cx43 are mediated by the interaction of its CT domain with other proteins, like Heat Shock Cognate Protein 70
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