TY - JOUR
T1 - A potential role for caveolin-1 in estradiol-17β-induced proliferation of mouse embryonic stem cells
T2 - Involvement of Src, PI3K/Akt, and MAPKs pathways
AU - Park, Jae Hong
AU - Lee, Min Young
AU - Han, Ho Jae
PY - 2009/3
Y1 - 2009/3
N2 - 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. Crown
AB - 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. Crown
KW - Caveolin
KW - Cell cycle
KW - Cell proliferation
KW - Embryonic stem cells
KW - Estradiol-17β
UR - http://www.scopus.com/inward/record.url?scp=58149289367&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2008.07.010
DO - 10.1016/j.biocel.2008.07.010
M3 - Article
C2 - 18694845
AN - SCOPUS:58149289367
SN - 1357-2725
VL - 41
SP - 659
EP - 665
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 3
ER -