gamma-radiation-induced growth arrest and apoptosis in p53-null lymphoma cells is accompanied by modest transcriptional changes in many genes
Details
Publication Year 2000-01,Volume 19,Issue #1,Page 29-37
Journal Title
DNA AND CELL BIOLOGY
Publication Type
Journal Article
Abstract
Damage to DNA produces cell cycle arrest, apoptosis, or both. The response in cells with p53 tumor suppressor function involves transcriptional changes, but whether that holds for cells lacking active p53, as in most tumors, is not known. Better characterization of the DNA damage response in tumors lacking p53 function is relevant to cytotoxic therapy. We have explored whether gamma-irradiated p53-null mouse T lymphoma cells undergo marked changes in transcription. Their arrest in G(2)/M prior to apoptosis required transcription. Transcripts whose abundance altered on irradiation mere sought by subtractive hybridization, and 1010 candidate clones from two oppositely enriched cDNA populations mere sequenced. Hybridization revealed small (<3-fold) increases or decreases in the transcripts of more than 15 genes, including some implicated in cell cycle control (e.g., BTG, Bap1) or apoptosis (e.g., STAT1, calpain), but no marked changes like those associated with other forms of T-cell death. Moreover, the expression of some critical apoptosis regulators, such as Bcl-2 family members, did not change. Hence, the G(2)/M arrest and apoptosis in the irradiated p53-null lymphoma appears to involve modest expression changes for many genes, but post-transcriptional alterations may be more critical.
Publisher
MARY ANN LIEBERT INC PUBL
Keywords
T-LYMPHOCYTES; DNA-DAMAGE; BCL-2; EXPRESSION; FAMILY; P53; IDENTIFICATION; SUPPRESSION; ACTIVATION; COMPONENT
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Creation Date: 2000-01-01 12:00:00
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