2007年4月
Epidermal growth factor directs sex-specific steroid signaling through Src activation
JOURNAL OF BIOLOGICAL CHEMISTRY
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- 巻
- 282
- 号
- 14
- 開始ページ
- 10697
- 終了ページ
- 10706
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1074/jbc.M610444200
- 出版者・発行元
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
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 5 alpha-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 5 alpha-dihydrotestosterone may be responsible for the different extent of observed cell growth.
- リンク情報
- ID情報
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- DOI : 10.1074/jbc.M610444200
- ISSN : 0021-9258
- PubMed ID : 17284441
- Web of Science ID : WOS:000245941000064