DECREASED CONNEXIN EXPRESSION AND INTERCELLULAR COMMUNICATION IN HUMAN BLADDER-CANCER CELLS

Connexins make up a gene family encoding proteins that form intercellu lar channels known as gap junctions. Decreases in connexin expression and loss of intercellular communication have been associated with the malignant phenotype in some animal and human cells. The expression of connexin 26 and 43 mRNA was evaluated in cultured normal and malignant human urothelial cells. The normal urothelial cells were shown by Nor thern analysis to express both connexins. Increased confluence of the cultured normal human urothelial cells was associated with upregulatio n of connexin 26 mRNA. Connexin 26 mRNA expression was decreased in th e bladder cancer cells. Using a human connexin 26 complementary DNA pr obe, nuclear run-on assays demonstrated that the decreased expression in the cancer cells was due to a failure of transcription. Southern bl ot analysis did not reveal any alterations in the genomic DNA. Assessm ent of gap junction function by scrape loading of lucifer yellow demon strated dye transfer in normal urothelial cells but not in bladder can cer cells. Downregulation of connexin 26 mRNA was associated with func tional loss of intercellular communication in the human bladder cancer cells. Connexin 43 expression varied considerably in the bladder canc er cell lines and did not correlate with dye transfer of lucifer yello w. These data suggest that alterations in the regulation of connexin 2 6 expression are associated with and may contribute to the malignant p henotype in bladder cancer.