Developmental and reproductive function of estrogen signaling

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Estrogen and its receptors (ERα and ERβ) are not only essential in female for normal function, but also necessary in male function such as reproductive tract, sexual behavior, maintenance of the skeleton, and cardiovascular system. In general, physiological estrogen action is regulated the transcription of estrogen responsive genes mediated by estrogen receptors. So far, the mechanism of specific estrogen action is still not clear. Simple question is what is estrogen action, and how to make specific estrogen action in vivo.In this experiment, we have focused on gain of function in mouse in vivo by using recombinant adenovirus vector and/or conditional transgenic mice, which expressed constitutive active form human ERα and ERβ, such as ca ERα and ERβ, respectively. Alternative strategy was "conditional gain of function" by using transgenic mice with Cre/loxP system. These transgenics were expressed the reporter genes (nlsGFP/DsRed2) before treated wo/Cre recombinase, were expressed the caERα and caERβ after treated w/Cre, respectively. It was possible to activate the estrogen signaling in the timing and organs selectively, treated with Cre recombinase.Finally, our goal is unveiled with the physiological role of estrogen signaling by through "selective gain/loss of function" in vivo. In this projects, we show that efp (estrogen responsive finger protein) is required for cell proliferation in mammary tumor by through the proteolysis 14-3-3 sigma which is negative regulator cell cycle (Nature, 417, 871-875, 2002).