Aberrant function and expression of gap junction proteins (connexins) during carcinogenesis

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(1) Aberrant expression of gap junction proteins (connexins[Cx]) during multistage mouse skin carcinogenesis (Carcinogenesis 16 : 1287-1297,1995)(a) Cx26 and Cx43 were differentially expressed in normal and surrounding non-tumorous epidermis. (b) In papillomasCx26 and Cx43 were frequently co-localized in the same gap junction plaques. (c) In squamous cell carcinomas, the expression of both Cx26 and Cx43 significantly decreased compared with surrounding non-tumourous epidermis. (d) The expression of Cx26 was reduced as cancer cells became morphologically less differentiated. (e) Squamous cell carcinomas at invasiv sites showed clear reduction of Cx26 and Cx43. (f) In squamous cell carcinomas metastasized into lymhph nodes, Cx26 was expressed, but few carcinoma cells expressed Cx43. (g) The localization of E-cadherin on the plasma membrane between cancer cells was maintained even at invasive and metastatic sites.(2) Aberrant expression, function and localization of connexins in human esophageal carcinoma cell lines (J Cancer Res Clin Oncol 120 : 445-453,1994)(a) Normal human esophageal tissue expressed both Cx26 and Cx43. (b) Most of the human esophageal carcinoma cell lines expressed lower amounts of Cx26 and Cx43 mRNAs than normal human esophageal tissues. (c) The co-expression of Cx26 and Cx43 mRNAs and proteins was observed only in two cell lines that showed a high level of GJIC and non-progressive tumor development. (d) E-cadherin was expressed in all cell lines.(3) Effect of a tumour promoter, DDT,on hepatic gap junctional intercellular communication in rats (Carcinogenesis 15 : 517-542,1994)DDT inhibited hepatic gap-junctional intercellular communication in vivo dose-dependently and changed Cx32 and Cx26 protein expression and localization.(4) Changes in the expression of connexins in hamster oral epithelium during wounnd healingDuring wound healing, the expression and localization of connexin proteins and transcripts were changed drastically.