We used microarray technology to compare mRNA decay rates of approximately 7000 transcripts in normal purified human T lymphocytes or the malignant T cell lines Jurkat and H9 following transcriptional arrest with actinomycin D. We found that over 2000 transcripts were expressed at abnormal levels in malignant T cells, including approximately 100 transcripts that were overexpressed and exhibited abnormally stable mRNA. Seventeen transcripts that encoded components of the ubiquitin-proteasome system were coordinately overexpressed and stabilized in both malignant cell lines. This pathway plays an important role in regulating cell growth and the development of malignancy. Numerous additional transcripts that encode proteins involved in growth regulation, damage repair and stress responses, posttranscriptional gene expression, and mitochondrial metabolism were also coordinately up-regulated and stabilized. Overall, our results suggest that abnormal mRNA stabilization in malignancy can lead to the overexpression of growth-regulatory genes and contribute to the malignant phenotype.
Bibliographical noteFunding Information:
Resources and staff of the Biomedical Genomics Center and the Supercomputing Institute at the University of Minnesota were critical for the completion of this work. We thank Nuzha Tahoe for critically reading the manuscript and Rachel Ogilvie for assistance with data analysis. We also thank Maria Hordinsky for obtaining biopsy samples from CTCL patients. This work was supported by grants from the Minnesota Medical Foundation to P.R.B. and K.A.B. and by NIH Grants AI49494 and AI52170.
Copyright 2008 Elsevier B.V., All rights reserved.
- Cutaneous T cell lymphoma
- Gene expression
- T cell
- T cell leukemia
- T lymphocyte
- mRNA decay
- mRNA stability