Abstract
There are several lines of evidence suggesting that connexin expression is suppressed and/or aberrantly localized in pre-cancerous lesions in several organs and many, if not all, tumor-promoting agents have been shown to inhibit gap junctional intercellular communication (GJIC) of cultured cells as well as those in vivo, suggesting that the loss of GJIC enhances clonal dispersion, causing loss of the growth-suppression signals from the surrounding cells. For endometrial carcinogenesis, it may be concluded that the loss of GJIC caused by the suppressed expression and the aberrant localization of connexin support the clonal evolution of endometrial cancer cells originating in the hyperplasia cells. In the present study, GJIC of IK-ER1, which overexpresses ER-alpha was markedly reduced in the estradiol-containing medium and the reduction was found to be inhibited by ICI182.780, a pure anti-estrogen substrate, as demonstrated by Lucifer-Yellow dye-transfer assay. Western blot analysis indicated that the expression of both Cx26 and Cx32 also decreased in E(+) and the reduction was inhibited by adding ICI182.780. These results supported the result of the dye-transfer assay. Thus, estrogen, which suppresses connexin expression of endometrial epithelium and causes cell proliferation, may act as a tumor-promoting agent for endometrium. [J Physiol Sci. 2006;56 Suppl:S30]
