Abstract
The TP73 gene is located at the chromosome 1p36 locus that is commonly disrupted or deleted in follicular lymphoma (FL) with poor prognosis. Therefore, we analyzed the expression of the pro-apoptotic TAp73 and anti-apoptotic ΔNp73 isoforms in cases of FL with normal or abnormal 1p36. We observed a significant increase in ΔNp73 expression and ΔNp73:TAp73 ratio, lower expression of cleaved caspase-3 and a higher frequency of Ki-67 and proliferating cell nuclear antigen (PCNA) positive cells in cases of FL with abnormal 1p36. A negative correlation between the ΔNp73:TAp73 ratio and cleaved caspase-3 expression, and a positive correlation between ΔNp73 expression and Ki-67 or PCNA, were observed. The expression of TAp73 and its pro-apoptotic transcriptional targets BIM. PUMA and NOXA were significantly lower in FL compared to reactive follicular hyperplasia. Together, our data demonstrate that 1p36 disruption is associated with increased ΔNp73 expression, decreased apoptosis and increased proliferation in FL.
Keywords:
Chromosome 1p36; follicular lymphoma; p73 isoforms.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / genetics
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Bcl-2-Like Protein 11
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Cell Proliferation
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Chromosome Aberrations*
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Chromosomes, Human, Pair 1*
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation, Neoplastic*
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Genetic Loci*
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Humans
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In Situ Hybridization, Fluorescence
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Lymphoma, Follicular / genetics*
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Lymphoma, Follicular / metabolism
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Lymphoma, Follicular / pathology
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Protein Isoforms
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Transcription, Genetic
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Tumor Protein p73
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Tumor Suppressor Proteins / genetics*
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Tumor Suppressor Proteins / metabolism
Substances
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Apoptosis Regulatory Proteins
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BBC3 protein, human
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BCL2L11 protein, human
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Bcl-2-Like Protein 11
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DNA-Binding Proteins
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Membrane Proteins
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Nuclear Proteins
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PMAIP1 protein, human
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Protein Isoforms
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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TP73 protein, human
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Tumor Protein p73
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Tumor Suppressor Proteins
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delta Np73 protein, human