Adaptive hypersensitivity following long-term estrogen deprivation: involvement of multiple signal pathways
Long-term estrogen deprivation causes hypersensitivity of MCF-7 cells to the mitogenic effect of estradiol (E 2) which is associated with activation of mitogen-activated protein kinase (MAPK). However, several lines of evidence indicate that MAPK activation is not the exclusive mechanism for E 2 hyp...
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Published in | Journal of steroid biochemistry and molecular biology Vol. 86; no. 3; pp. 265 - 274 |
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Main Authors | , , , , |
Format | Journal Article Conference Proceeding |
Language | English |
Published |
Oxford
Elsevier Ltd
01.09.2003
Elsevier Science |
Subjects | |
Online Access | Get full text |
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Summary: | Long-term estrogen deprivation causes hypersensitivity of MCF-7 cells to the mitogenic effect of estradiol (E
2) which is associated with activation of mitogen-activated protein kinase (MAPK). However, several lines of evidence indicate that MAPK activation is not the exclusive mechanism for E
2 hypersensitivity and multiple signal pathways might be involved. The current study explores the possible role of the PI3 kinase (PI3K) pathway in development of E
2 hypersensitivity. Basal PI3K activity in long-term estrogen deprived MCF-7 cells (LTED) was elevated as evidenced by increased phosphorylation of three downstream effectors, Akt, p70 S6 kinase, and eukaryotic initiation factor-4E binding protein (4E-BP1), which was blocked by the specific inhibitor of PI3K, LY294002. Dual blockade of both MAPK and PI3K completely reversed E
2 hypersensitivity of LTED cells. Enhancement in aromatase activity is another phenomenon accompanied with E
2 hypersensitivity. In aromatase over-expressing MCF-7 cells, aromatase activity was reduced by inhibitors of MAPK and PI3K suggesting the involvement of protein phosphorylation in the regulation of aromatase activity. Our data suggest that in addition to the MAP kinase pathway, activation of the PI3 kinase pathway is involved in E
2 hypersensitivity, which develops during adaptation of MCF-7 cells to the low estrogen environment. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0960-0760 1879-1220 |
DOI: | 10.1016/S0960-0760(03)00366-2 |