Abstract
The c-Src tyrosine kinase has been implicated to play an integral role in modulating growth factor receptor, integrin and steroid receptor function. One class of steroid receptors that c-Src modulates is the estrogen receptor alpha (ERalpha). Although there is strong biochemical evidence supporting a role for c-Src in ERalpha signaling, the consequence of this association is unclear at the biological level. To explore the significance of c-Src in ERalpha signaling, we studied the development of various reproductive organs that are dependent on ERalpha in c-Src-deficient mice. We show that the loss of the c-Src tyrosine kinase correlates with defects in ductal development as well as in uterine and ovarian development. Genetic and biochemical analyses of c-Src-deficient mammary epithelial cells also revealed defects in the ability of mammary epithelial cells to activate a number of signaling pathways in response to exogenous estrogen stimulation. Taken together, these studies demonstrate that c-Src plays a role in ERalpha signaling in vivo.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Line, Tumor
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Cyclin D1 / metabolism
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Enzyme Activation / drug effects
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Epithelium / drug effects
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Epithelium / metabolism
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Estrogen Receptor alpha / metabolism*
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Estrogens / pharmacology
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Female
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Mammary Glands, Animal / abnormalities
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Mammary Glands, Animal / growth & development*
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Mammary Glands, Animal / metabolism*
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinases / metabolism
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Ovary / metabolism
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Phenotype
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Receptors, Estrogen / metabolism
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Signal Transduction*
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Uterus / metabolism
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src-Family Kinases / deficiency*
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src-Family Kinases / genetics
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src-Family Kinases / metabolism*
Substances
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Estrogen Receptor alpha
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Estrogens
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Proto-Oncogene Proteins
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Receptors, Estrogen
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Cyclin D1
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src-Family Kinases
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Glycogen Synthase Kinase 3 beta
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases
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Glycogen Synthase Kinase 3