Connexin

Different cells express different connexin isoforms, which make for great variations in binding affinities between different hemi-connexons. Connexons do form between cells of different types but not all heterogeneous hemi-connexon combinations support the formation of connexons between different cells. This may be... 

Kenne K, Fransson-Steen R, Honkasalo S, et al. 1994. Two inhibitors of gap junctional intercellular communication, TPA and endosulfan Different effects on phosphorylation of connexin 43 in the rat liver epithelial cell line, lAR 20. Carcinogenesis 15(6) 1161-1165. 

New information has been added in appropriate chapters on hpid rafts and caveolae, aquaporins, connexins, disorders due to mutations in genes encoding proteins involved in intracellular membrane transport, absorption of iron, and conformational diseases and pharmacogenomics. 

Bertram, J. S. 2004. Induction of connexin 43 by carotenoids Functional consequences. Arch Biochem Biophys 430(1) 120-126. 

King, T. J. and J. S. Bertram. 2005. Connexins as targets for cancer chemoprevention and chemotherapy. Biochim Biophys Acta 1719(1-2) 146-160. 

Rogers, M., J. M. Berestecky, M. Z. Hossain et al. 1990. Retinoid-enhanced gap junctional communication is achieved by increased levels of connexin 43mRNA and protein. Mol Carcinog 3(6) 335-343. 

Connexin 43 is one of the cell membrane gap junction proteins that allow for cell to cell communication. Cancer cell transformation is correlated with the loss of Connexin 43 expression (Hussain et al. 1989, Zhang et al. 1992). Lycopene increased Connexin 43 expression in fetal skin fibroblasts (Stahl et al. 2000), oral cancer KB-1 cells grown in organotypic rafts (Livny et al. 2003) and breast cancer cell lines (Chalabi et al. 2007). 

Forbes et al. saw a slight up-regulation of Connexin 43 in PC-3 cells (androgen unresponsive) with pure lycopene treatment but no Connexin 43 expression (with or without lycopene) in the highly metastatic PC-3MM2 variant (Table 21.2) indicating that with increasing metastatic conversion either the ability to turn on Connexin 43 is lost and/or the receptors responsive to lycopene are lost (Forbes et al. 2003). 

Chen, JT, YW Cheng, MC Chou et al. 2003. The correlation between aberrant connexin 43 mRNA expression induced by promoter methylation and nodal micrometastasis in non-small cell lung cancer. Clin Cancer Res 9 4200-4204. 

Forbes, K, K Gillette, and I Sehgal. 2003. Lycopene increases urokinase receptor and fails to inhibit growth or connexin expression in a metastatically passaged prostate cancer cell line a brief communication. Exp Biol Med 228 967-971. 

Gitenay, D, B Lyan, J Talvas, A Mazur, S George, C Caris-Veyrat, and E Rock. 2007. Serum from rats fed red or yellow tomatoes induced Connexin-43 expression independently from lycopene in a prostate cancer cell line. Biochem Biophys Res Commun 364 578-582. 

Vine, AL, YM Leung, and JS Bertram. 2005. Transcriptional regulation of connexin 43 expression by retinoids and carotenoids similarities and differences. Mol Carcinog 43 75-85. 

Zhang, LX, RV Cooney, and JS Bertram. 1992. Carotenoids up-regulate Connexin 43 expression independent of their provitamin A or antioxidant properties. Cancer Res 52 5707-5712. 

It has been shown that the expression of connexin 43 (Cx43) is upregulated by cancer-preventive retinoids and carotenoids, which correlate with the suppression of carcinogen-induced transformation in 10T1/2 cells. Recently, it has been reported that Cx43 induction by astaxanthin, but not by a RAR-specific retinoid, was inhibited by GW9662, a PPARy antagonist (Bertram et al., 2005). 

Although the influence of lycopene and proliferation of carcinoma cells appears not limited to its ability to modulate Cx43 expression, lycopene as well as its oxidation products have been reported to enhance GJC in cultured cells (Livny et al., 2002 Stahl et al., 2000). Recent data indicate that lycopene may indeed increase connexin-43 expression in human prostate (Kucuk et al., 2001). 

Vine, A.L. and Bertram, J.S. 2005. Up-regulation of connexin 43 by retinoids but not by non-provitamin A carotenoids requires RARs. Nutr Cancer 52 105-113. 

Lauf, U., Lopez, P. and Falk, M. M. (2001). Expression of fluorescently tagged connexins A novel approach to rescue function of oligomeric DsRed-tagged proteins. FEBS Lett. 498, 11-5. 

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