Activation of Wnt/beta-catenin/Tcf signaling pathway in human astrocytomas.
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/beta-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/beta-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, beta-catenin, c-myc and cyclin D1 and protein levels of beta-catenin, Lef1, Tcf4, c-Myc, N-Myc, c-jun and cyclin D1. RT-PCR analysis demonstrated the overexpression of Dvl-3, beta-catenin, c-myc and cyclin D1 in astrocytomas. Western blotting revealed upregulation of beta-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 beta-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/beta-catenin/Tcf signaling pathway is implicated in malignancy of astrocytomas.
Sareddy
Gangadhara Reddy
GR
Department of Biotechnology and Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
Panigrahi
Manas
M
Challa
Sundaram
S
Mahadevan
Anita
A
Babu
Phanithi Prakash
PP
D000293:Adolescent; D000328:Adult; D001254:Astrocytoma / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin