A potential role for caveolin-1 in estradiol-17beta-induced proliferation of mouse embryonic stem cells: involvement of Src, PI3K/Akt, and MAPKs pathways.
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-17beta (E(2)) and caveolin-1 in mouse ES cell proliferation. E(2) 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 E(2)-induced increase in caveolin-1 and caveolin-2 proteins expression. E(2) 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 E(2)-induced increase in caveolin-1 expression and the accompanying [(3)H]-thymidine incorporation. Furthermore, inhibition of caveolin-1 expression using a caveolin-1 siRNA significantly attenuated E(2)-induced up-regulation of proto-oncogenes, cell cycle regulatory proteins, [(3)H]-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, E(2) stimulates mouse ES cell proliferation partially through up-regulating caveolin-1 via the Src, PI3K/Akt, ERK1/2 signaling pathways.
Park
Jae Hong
JH
Department of Veterinary Physiology, Biotherapy Human Resources Center (BK21), College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Lee
Min Young
MY
Han
Ho Jae
HJ
D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011743:Pyrimidines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
C412373:AG 1879; D051242:Caveolin 1; D018797:Cell Cycle Proteins; D002867:Chromones; D004965:Estrogen Antagonists; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011743:Pyrimidines; D034741:RNA, Small Interfering; D000077267:Fulvestrant; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004958:Estradiol; D019061:src-Family Kinases