Coordinate stabilization of growth-regulatory transcripts in T cell malignancies.
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.
Vlasova
Irina A
IA
Department of Microbiology, University of Minnesota, 420 Delaware Street, SE, 1315 Mayo Building, Minneapolis, MN 55455, USA.
McNabb
Jennifer
J
Raghavan
Arvind
A
Reilly
Cavan
C
Williams
Darlisha A
DA
Bohjanen
Kimberly A
KA
Bohjanen
Paul R
PR
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000235:genetics* / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation
D019384:Nucleic Acid Synthesis Inhibitors; D010455:Peptides; D012333:RNA, Messenger; D025801:Ubiquitin; D003609:Dactinomycin; D012313:RNA; D046988:Proteasome Endopeptidase Complex