Protein Arginine Methyltransferase 5 Is Highly Expressed in Glioblastoma and Important for the Growth of Glioma Cells
Rong Li, Xinyang Zhao, Dewang Zhou, Qiang Ding, Peter H King, G Yancey Gillespie, L Burt Nabors, Xiaosi Han. University of Alabama at Birmingham, Birmingham, AL
Background: Protein Arginine Methytransferase 5 (PRMT5) is a type II protein arginine methyltranferase that catalyzes transfer of methyl groups from S-adenosyl methionine to the arginine residues on histones or non-histone proteins. PRMT5 is involved in a variety of biological processes such as transcriptional regulation, RNA splicing and signal transduction. Recent studies demonstrate that PRMT5 is highly expressed in some types of tumor cells including leukemia, colon, lung and prostate cancer and may serve an important functional role. However, the expression of PRMT5 in astrocytomas and the role of PRMT5 in tumor progression have not been investigated.
Design: We performed PRMT5 immunostaining on paraffin blocks of 20 cases of astrocytomas of different grades (10 glioblastoma, 5 WHO II diffuse astrocytoma, 5 anaplastic astrocytoma, and on 10 epilepsy brains. The intensity (0-3) and percentage of tumor cell staining were multiplied to determine an H-score. In addition, we knocked down the expression PRMT5 in glioma cell lines and determined the effect on cell growth.
Results: PRMT5 was undetectable in astrocyte while expressed in neuron of control brain sections. The expression of PRMT5 was undetectable in WHO II astrocytomas as well. However, the expression of PRMT5 was significantly higher in high grade astrocytomas (p<0.001). Among high grade astrocytomas, PRMT5 expression was significantly higher in glioblastoma than in anaplastic astrocytoma (p<0.001). Interestingly, PRMT5 immunostaining appears heterogeneous throughout the tumor tissues and has a predominantly nuclear positivity in GBM cells. Furthermore, upregulated cytoplasmic expression of PRMT5 was identified in the endothelial cells of the microvasculature in glioblastoma. Knocking down of PRMT5 in U251 and LN229 significantly inhibited cancer cell growth.
Conclusions: PRMT5 is important for glioma cell growth and may be a marker of malignancy in tumors of glial origin.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 265, Monday Morning