Activation of Wnt/β-catenin/Tcf signaling pathway in human astrocytomas

Gangadhara Reddy Sareddy, Manas Panigrahi, Sundaram Challa, Anita Mahadevan, Phanithi Prakash Babu

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Astrocytomas are the most common form of primary brain tumors. Understanding the molecular basis of development and progression of astrocytomas is required to develop more effective therapies. Although, over activation of Wnt/β-catenin/Tcf pathway is a hallmark of several forms of cancer, little is known about its role in human astrocytomas. Here, we report the evidence that Wnt/β-catenin/Tcf signaling pathway is constitutively activated in astrocytic tumors. In the present study, human astrocytic tumors with different clinical grades were analyzed for mRNA expression of Dvl-1, Dvl-2, Dvl-3, β-catenin, c-myc and cyclin D1 and protein levels of β-catenin, Lef1, Tcf4, c-Myc, N-Myc, c-jun and cyclin D1. RT-PCR analysis demonstrated the overexpression of Dvl-3, β-catenin, c-myc and cyclin D1 in astrocytomas. Western blotting revealed upregulation of β-catenin, Lef1, Tcf4 and their target proteins in the core tumor tissues in comparison to peritumor and normal brain tissues. The protein and mRNA levels were positively correlated with the histological malignancy. Cytoplasmic and nuclear accumulation of β-catenin, nuclear localization of Lef1, Tcf4, c-Myc, N-Myc, c-jun and cyclin D1 were demonstrated by immunohistochemical staining. Our studies tend to suggest that Wnt/β-catenin/Tcf signaling pathway is implicated in malignancy of astrocytomas.

Original languageEnglish (US)
Pages (from-to)307-317
Number of pages11
JournalNeurochemistry International
Volume55
Issue number5
DOIs
StatePublished - Sep 1 2009

Keywords

  • Astrocytomas
  • Histological malignancy
  • Signaling pathway
  • Tumor
  • Wnt
  • β-Catenin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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    Sareddy, G. R., Panigrahi, M., Challa, S., Mahadevan, A., & Babu, P. P. (2009). Activation of Wnt/β-catenin/Tcf signaling pathway in human astrocytomas. Neurochemistry International, 55(5), 307-317. https://doi.org/10.1016/j.neuint.2009.03.016