Akt activation by estrogen in estrogen receptor-negative breast cancer cells

It has been a common belief that estrogen regulates cellular responses through binding to its receptor, the estrogen receptor (ER). In the nucleus, estrogen modulates the expression of estrogen-responsive genes through the action of the ER at the transcriptional level. In the cytoplasm, the ER-depen...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-12, Vol.61 (23), p.8390-8392
Main Authors: TSAI, Eing-Mei, WANG, Shao-Chun, LEE, Jau-Nan, HUNG, Mien-Chie
Format: Article
Language:English
Subjects:
Biological and medical sciences
Breast Neoplasms - enzymology
Breast Neoplasms - metabolism
Enzyme Activation - drug effects
Estrogen Receptor alpha
Estrogens - pharmacology
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
Phosphatidylinositol 3-Kinases - metabolism
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Receptors, Estrogen - physiology
Tumor Cells, Cultured
Tumors
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Summary:It has been a common belief that estrogen regulates cellular responses through binding to its receptor, the estrogen receptor (ER). In the nucleus, estrogen modulates the expression of estrogen-responsive genes through the action of the ER at the transcriptional level. In the cytoplasm, the ER-dependent signaling pathway has been shown to be involved in the activation of Akt and the downstream molecules. It is not clear, however, whether estrogen can modulate cytoplasmic signaling in an ER-independent manner. Human breast cancer cell lines without detectable ERs such as MDA-MB-435 and MDA-MB-231 were treated in estrogen-depleted medium followed by a brief treatment with estrogen. The activation of Akt was evaluated by a phosphoserine antibody. Our results showed that estrogen stimulated Akt activation, as indicated by phosphorylation at Ser(473) of the oncoprotein, in ER-negative breast cancer cells. Activation of Akt by estrogen in these cells was time and dose dependent and could be blocked by inhibitors of phosphatidylinositol 3'-kinase and Src kinase but not by estrogen antagonists. Our results provide evidence as well as the mechanism of the receptor-independent function of estrogen, in which the antiapoptotic factor Akt is activated.
ISSN:0008-5472
1538-7445