Estrogen-dependent c-jun upregulation may control cyclin D1 expression

Excerpt

Estrogen controls the proliferation of estrogen-receptor positive breast cancer cells. In an effort to understand how estrogen promotes cell-cycle progression we and others have found that expression of the cell-cycle regulator cyclin D1 is tightly controlled by estrogen in MCF-7 cells. However, stable expression of the estrogen receptor in different cell lines is not sufficient to allow estrogen-dependent cyclin D1 expression. This lack of cyclin D1 upregulation in cells stably expressing estrogen receptor (ER) may explain why estrogen cannot induce proliferation in these cells. To further understand the molecular mechanisms by which cyclin D1 is regulated in response to estrogen, we have characterised in more detail the response of HaCaT cells expressing ER to estrogen, and compared them with those observed by MCF-7. Differential activation of AP-1 members is seen after estrogen treatment of MCF-7. This MCF-7 specific upregulation of c-fos and c-jun precedes and correlates well with cyclin D1 induction by estrogen. Further studies using the cyclin D1 promoter indicate that c-jun upregulation by estrogen may induce cyclin D1 expression and most likely cell cycle progression. Therefore, we suggest that the ability of MCF-7 cells to activate c-jun in response to estrogen is crucial to understanding the estrogen-dependent proliferation of breast cancer cells. …