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Shc3 affects human high-grade astrocytomas survival.
Lorenzo Magrassi1, Luciano Conti, Andrea Lanterna
1Neurochirurgia, Dipartimento di Chirurgia, Università di Pavia, IRCCS Policlinico S. Matteo, and IGM CNR, P.le Golgi 2, Pavia 27100, Italy. magrassi@igm.cnr.it
Oncogene
|May 5, 2005
Summary
In human glioblastomas, the normal Shc gene expression pattern is disrupted, with both Shc1 and Shc3 proteins co-expressed. Inhibiting Shc3 in glioma cells impairs survival, suggesting Shc molecules are key to glioblastoma growth.
Area of Science:
- Molecular Biology
- Neuroscience
- Oncology
Background:
- Shc1 and Shc3 proteins exhibit distinct expression patterns during neuronal development, with Shc1 in progenitor cells and Shc3 in mature neurons.
- Normally, Shc3 is not expressed in glial cells.
Purpose of the Study:
- To investigate the expression patterns of Shc1 and Shc3 in human astrocytomas and glioblastomas.
- To determine the role of Shc3 in glioblastoma cell growth and survival.
Main Methods:
- Analysis of Shc1/Shc3 expression in human tumor samples and primary glioblastoma cultures.
- Assessment of Shc3 phosphorylation status in vivo.
- Functional studies using dominant-negative Shc3 variants in high-grade glioma cells.
Main Results:
- Human astrocytomas and glioblastomas show aberrant co-expression of Shc1 and Shc3.
- Shc3 is highly expressed in glioblastoma, a proliferative tumor lacking neuronal differentiation.
- Inhibition of Shc3 in vitro decreased Akt phosphorylation and increased apoptosis, impairing cell survival.
Conclusions:
- The Shc1/Shc3 expression switch is subverted in glioblastomas.
- Shc3 plays a significant role in glioblastoma cell proliferation and survival.
- Targeting Shc molecules may offer therapeutic potential for high-grade gliomas.