Title:Down Regulated Expression of Claudin-1 and Claudin-5 and Up Regulation of β-Catenin: Association with Human Glioma Progression
Volume: 13
Issue: 8
Author(s): Hanuma K. Karnati, Manas Panigrahi, Noor A. Shaik, Nigel H. Greig, S. Appala R. Bagadi, Mohammad A. Kamal and Nagaiah Kapalavayi
Affiliation:
Keywords:
Adheren junction, claudin 1 (CLDN1), claudin 5 (CLDN5), β-catenin, glioma, Glioblastoma multiforme (GBM),
tight junction (TJ).
Abstract: Glioblastoma multiforme is the most common form of intracranial malignancy in humans, and is characterized
by aggressive tumor growth, tissue invasion and neurodegenerative properties. The present study investigated the
expression status of tight junction associated Claudin 1 (CLDN1), Claudin 5 (CLDN5) and Adheren junction associated β-
catenin genes in the light of their critical role in the progression of both low- and high-grade human gliomas. Using
quantitative PCR and Western blot methods the mRNA and protein status of CLDN1, CLDN5 and β-catenin genes were
studied in a total of 25 human gliomas of World Health Organization (WHO) grades I-IV, non-cancerous control brain
tissues and their corresponding model cell lines (C6, U373, U118, T98 and U87MG). Quantitative analysis of the
transcript and protein expression data showed that CLDN1 and CLDN5 were significantly down regulated (p=<0.001) in
tumors of all four grades and model cell lines. This decrease in expression pattern was in accordance with the increasing
grade of the tumor. A 4-fold stronger reduction of CLDN1 when compared to CLDN5 was evident in high-grade tumors.
Interestingly, β-catenin was up regulated in all tumor types we studied (p=<0.005). Our findings, suggest that down
regulated CLDN1 and CLDN5 genes have potential relevance in relation to the progression of glioblastoma multiforme.
Hence, their therapeutic targeting may provide both insight and leads to control the cellular proliferation and subsequent
invasiveness among affected individuals.
