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The autocrine loop of TGF-α/EGFR and brain tumors

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Abstract

Malignant human gliomas are the most common formsof primary tumors in the central nerve system.Due to their location and invasive nature, treatmentso far has been mainly palliative. Thus, understandingthe molecular detail of tumor transformation and progressionis crucial for developing effective therapeutic strategy forthis fetal tumor. Among the genetic alternations foundin these tumors, p53 inactivation and PDGF/PDGFR activationrepresent the early events, and the loss ofchromosome 10 and gene amplification and rearrangement ofEGFR represent the late events. Studies with bothglioma cell lines and primary tumor tissues havestrongly suggested that TGF-α and EGFR function asan important autocrine loop in supporting proliferation ofhuman glioma, especially in high grade glioma, sinceelevated TGF-α expression is also found in thesehigh grade tumors. Furthermore, down regulation of theexpression of TGF-α by antisense constructs has beenshown to inhibit several types of human tumorcell growth including glioma. Other means of therapeuticapproaches using this autocrine loop as a targetalso include the use of monoclonal antibodies andtheir cytotoxic conjugated. Considerable understanding of the EGFR-mediatedsignal transduction pathways has become available recently, whichincluding GRB2/mSOS1 mediated MAP kinase activation; JAK/STATs pathway;PLC-γ pathway. However, much work still needs tobe done before a specific component of thesepathways can be applied for effective control oftumor growth in the clinic.

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  1. Department of Neuro-Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, 77030, USA

    Ping Tang, Peter A. Steck & W.K. Alfred Yung

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Tang, P., Steck, P.A. & Yung, W.A. The autocrine loop of TGF-α/EGFR and brain tumors. J Neurooncol 35, 303–314 (1997). https://doi.org/10.1023/A:1005824802617

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