Epidermal growth factor directs sex-specific steroid signaling through Src activation.

Estrogens and androgens exert many biological effects that do not require interactions of their receptors with chromosomal DNA. However, it has been a long-standing question how the sex steroid receptors provoke signal transduction outside the nucleus. Here we have shown that epidermal growth factor (EGF) directs sex-specific steroid signaling through ...
Src activation. We have revealed that estrogen (E2)-induced Src activation takes place in, not only plasma, but also endomembranes. This was found ascribed to the existence of EGF and the occurrence of EGF receptor (EGFR)-involved endocytosis of estrogen receptor together with Src. EGFR, estrogen receptor, and Src were found to form a complex upon E2 stimulation. The cell growth of breast cancer-derived MCF-7 cells was found to remarkably increase through the above EGF-involved estrogen-signaling process. In contrast, the androgen 5alpha-dihydrotestosterone-induced Src activation occurs only in the plasma membrane free from the interaction of EGFR with androgen receptor, irrespective of EGF. The cell growth occurred only moderately as a result. The spatial difference in Src activation between E2 and 5alpha-dihydrotestosterone may be responsible for the different extent of observed cell growth.
Mesh Terms:
Animals, Breast Neoplasms, Cell Line, Tumor, Cytoplasm, Dihydrotestosterone, Endocytosis, Enzyme Activation, Epidermal Growth Factor, Estrogens, Female, Intracellular Membranes, Mice, Multiprotein Complexes, Receptor, Epidermal Growth Factor, Receptors, Androgen, Receptors, Estrogen, Sex Characteristics, Signal Transduction, src-Family Kinases
J. Biol. Chem.
Date: Apr. 06, 2007
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