A potential role for caveolin-1 in estradiol-17β-induced proliferation of mouse embryonic stem cells: Involvement of Src, PI3K/Akt, and MAPKs pathways

Abstract

Although both estrogen and caveolin have been implicated in many physiological functions, their precise relationship is not completely understood in mouse embryonic stem (ES) cells. Thus, this study was designed to examine the relationship between estradiol-17β (E2) and caveolin-1 in mouse ES cell proliferation. E2 increased the expression of caveolin-1 and caveolin-2 mRNA and proteins, but pre-treatment with ICI 182,780 [an estrogen receptor (ER) antagonist] inhibited E2-induced increase in caveolin-1 and caveolin-2 proteins expression. E2 also increased phosphorylated levels of caveolin-1, Src, and Akt. Phospho-caveolin-1 was significantly blocked by ICI 182,780 or pyrazolopyrimidine 2 (PP2; a Src-kinase inhibitor). LY 294002 (a PI3K inhibitor) or PD 98059 (an ERK1/2 inhibitor) prevented E2-induced increase in caveolin-1 expression and the accompanying [3H]-thymidine incorporation. Furthermore, inhibition of caveolin-1 expression using a caveolin-1 siRNA significantly attenuated E2-induced up-regulation of proto-oncogenes, cell cycle regulatory proteins, [3H]-thymidine incorporation, overall cell number, and percent of the cell population in S phase, while mediating a concomitant increase in the G0/G1 population. In conclusion, E2 stimulates mouse ES cell proliferation partially through up-regulating caveolin-1 via the Src, PI3K/Akt, ERK1/2 signaling pathways.