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

Taro Hitosugi, Kazuki Sasaki, Moritoshi Sato, Yoshiko Suzuki, Yoshio Umezawa

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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. Wehave 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 α-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 5α-dihydrotestosterone may be responsible for the different extent of observed cell growth.

Original languageEnglish (US)
Pages (from-to)10697-10706
Number of pages10
JournalJournal of Biological Chemistry
Issue number14
StatePublished - Apr 6 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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