Article: Cell cycle regulation of breast cancer cells through estrogen-induced activities of ERK and Akt protein kinases.
Molecular and cellular endocrinology
2005 Volume 237, Issue 1-2, Page(s) 11–23
Abstract: The proliferative effect of estrogens on breast cancer cell (BCC) is mainly mediated through estrogen receptors (ER). Non-transcriptional effects of estrogens, exerted through activation of several protein kinases, may also contribute to BCC ... ...
| Abstract | The proliferative effect of estrogens on breast cancer cell (BCC) is mainly mediated through estrogen receptors (ER). Non-transcriptional effects of estrogens, exerted through activation of several protein kinases, may also contribute to BCC proliferation. However, the relative contribution of these two responses to BCC proliferation is not known. We characterized a novel estrogenic receptor ligand which possess Akt and ERK activating properties distinct from that of 17beta-estradiol. Early and delayed waves of activation of these kinases were detected upon estrogenic challenge of BCC, but only molecules able to promote a significant, delayed activation of ERK-induced BCC proliferation. Estrogen-induced cell cycle progression was not sensitive to the inhibition of ERK-regulating kinases MEK1 and 2. ERalpha was found to be necessary, but not sufficient for kinases activation. Thus, estrogens elicit a distinct pattern of early and delayed activation of ERK and Akt, and early protein kinase activation is probably not involved in BCC proliferation. Structural variations in the estrogen molecule may confer novel biological properties unrelated to estrogen-dependent transcriptional activation. |
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| MeSH term(s) | Breast Neoplasms/enzymology ; Breast Neoplasms/pathology ; Cell Cycle/drug effects ; Estradiol/pharmacology ; Female ; Humans ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Tumor Cells, Cultured |
| Chemical Substances | Proto-Oncogene Proteins ; Estradiol (4TI98Z838E) ; AKT1 protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase 3 (EC 2.7.11.24) |
| Language | English |
| Publishing date | 2005-06-15 |
| Publishing country | Ireland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 187438-x |
| ISSN | 1872-8057 ; 0303-7207 |
| ISSN (online) | 1872-8057 |
| ISSN | 0303-7207 |
| DOI | 10.1016/j.mce.2005.04.003 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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