17β-Estradiol induces ERβ up-regulation via p38/MAPK activation in colon cancer cells

Estrogen receptors (ERα and ERβ) mediate opposite functions on cancer growth induced by 17β-estradiol (E2). E2 binding to ERα induces a cancer promoting response, whereas E2 binding to ERβ exerts a protective action against cancer growth. Moreover, E2 can diversely modulate the ERα and ERβ levels intensifying or decreasing their actions in target tissues. Only molecular mechanisms at the root of E2 ability to down-regulate the ERα levels are known. Here, we report the first molecular mechanism underlying E2-induced ERβ up-regulation in DLD-1 colon cancer cells. E2 induces a short term (2 and 4 h after stimulation) translation of ERβ mRNA followed by a late (24 h after stimulation) enhanced transcription. Both processes required the E2-induced persistent and palmitoylation-dependent p38/MAPK activation. Overall, our data suggest a finely tuned control exerted by rapid signals on different cellular molecular events important for the protective effects of E2 against colon cancer growth.