Direct modulation of tumor suppressor connexin 26 gene by human chorionic gonadotropin in rat mammary glands

Human chorionic gonadotropin (hCG) has been shown to reduce the incidence of carcinogen-induced rat mammary tumors. Because connexin 26 (Cx26), a tumor suppressor gene candidate, can be up-regulated in mammary epithelial cells during lactation, we examined the in vivo and ex vivo effects of hCG on Cx26 expression in rat mammary tissues and used its effect on the expressions of beta-casein and Cx43 as controls. The Cx26 mRNA and protein expressions were up-regulated by daily administrations of 100 units of hCG, starting on day 5 and reaching a 14-fold maximum increment on days 16 through 21. It remained elevated above the basal level even 20 days after hCG withdrawal. The changes in beta-casein expression ran parallel to that of Cx26, whereas the expression of Cx43 was down-regulated. There was no correlation between steroidal hormone levels and Cx26 expression, except for the first 5 days of hCG treatment. In the ex vivo organ culture system, exposure of mammary glands to 10 units/ml hCG for 5 days up-regulated Cx26 but had no effect on beta-casein expression. These results imply a direct induction of the tumor suppressor Cx26 gene by hCG in mammary epithelial cells, a mechanism unrelated to lactation.