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Molecular mechanism of a cross-talk between estrogen and growth-factor signaling pathways
S Kato1, T Kitamoto, Y Masuhiro
1Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan. uskato@hongo.ecc.u-tokyo.ac.jp
Abstract:
The actions of estrogen (E2) are considered to be mediated through its nuclear E2 receptor (ER). In cancer development, growth factors are shown to act synergistically with E2. Recently, we found that the mitogen-activated protein kinase, activated by growth factors, phosphorylates human ERalpha and this phosphorylation potentiates the transactivation function of human ERalpha demonstrating a novel cross-talk between E2 and growth factor-signaling pathways. In this review, the molecular mechanism of this cross-talk is discussed.
Insights
Estrogen (E2) actions involve its receptor (ER). Growth factors enhance E2
Area of Science:
- Molecular Endocrinology
- Cancer Biology
- Signal Transduction
Background:
- Estrogen (E2) exerts its effects via the nuclear estrogen receptor (ER).
- Growth factors can synergize with E2 in cancer development.
- Cross-talk between E2 and growth factor signaling pathways is crucial in biological processes.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the cross-talk between estrogen and growth factor signaling pathways.
- To investigate how growth factor-activated signaling affects estrogen receptor (ER) function.
Main Methods:
- Focuses on the phosphorylation of human ERalpha by mitogen-activated protein kinase (MAPK).
- Discusses the functional consequences of this phosphorylation event on ERalpha transactivation.
- Reviews the molecular interplay between growth factor and E2 signaling.
Main Results:
- Growth factor-activated mitogen-activated protein kinase phosphorylates human ERalpha.
- This phosphorylation enhances the transactivation function of human ERalpha.
- Demonstrates a novel cross-talk mechanism between E2 and growth factor signaling.
Conclusions:
- Estrogen and growth factor signaling pathways exhibit significant cross-talk.
- Phosphorylation of ERalpha by MAPK is a key mechanism in this cross-talk.
- Understanding this interaction is vital for cancer research and therapeutic strategies.