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Akt is involved in the inhibition of cell proliferation by EGF
Soung Hoo Jeon1, Woo-Jeong Jeong, Jae-Young Cho
1Department of Biotechnology, Yonsei University, Seoul 120-752, Korea.
Abstract:
Axin is a negative regulator of the Wnt/beta-catenin pathway and is involved in the regulation of axis formation and proliferation. Involvement of Axin in the regulation of other signaling pathways is poorly understood. In this study, we investigated the involvement of Akt in growth regulation by Axin in L929 fibroblasts stimulated by EGF. Akt activity was increased by EGF treatment and Ras activation, respectively. Both the EGF- and Ras-induced Akt activations were abolished by Axin induction, as revealed by both Western blot and immunocytochemical analyses. The proliferation and Akt activation induced by EGF were decreased by Axin induction, and the effects of EGF were abolished by treatment of an Akt-specific inhibitor. Therefore, Axin inhibits EGF-induced proliferation of L929 fibroblasts by blocking Akt activation.
Insights
Axin protein inhibits fibroblast proliferation by blocking Akt activation, a key pathway stimulated by epidermal growth factor (EGF). This study clarifies Axin's role in growth regulation beyond the Wnt/beta-catenin pathway.
Area of Science:
- Cellular Biology
- Molecular Biology
- Signal Transduction
Background:
- Axin is a known negative regulator of the Wnt/beta-catenin pathway, impacting cell proliferation and axis formation.
- The role of Axin in regulating other signaling pathways, particularly in response to growth factors, remains largely unexplored.
Purpose of the Study:
- To investigate the role of Akt in Axin-mediated growth regulation in L929 fibroblasts stimulated by epidermal growth factor (EGF).
- To elucidate the mechanism by which Axin affects EGF-induced proliferation and Akt activation.
Main Methods:
- Utilized Western blot and immunocytochemical analyses to assess Akt activation.
- Examined the effects of Axin induction on EGF- and Ras-induced Akt activation.
- Investigated the impact of Axin on EGF-induced fibroblast proliferation, including experiments with an Akt-specific inhibitor.
Main Results:
- EGF and Ras activation increased Akt activity in L929 fibroblasts.
- Axin induction abolished both EGF- and Ras-induced Akt activations.
- Axin induction decreased EGF-stimulated proliferation and Akt activation, effects reversed by an Akt inhibitor.
Conclusions:
- Axin negatively regulates EGF-induced proliferation in L929 fibroblasts.
- Axin exerts its inhibitory effect by blocking Akt activation, highlighting a novel role for Axin in growth factor signaling.
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