PMID- 14565663 OWN - NLM STAT- MEDLINE DCOM- 20040323 LR - 20190116 IS - 1042-8194 (Print) IS - 1026-8022 (Linking) VI - 44 IP - 9 DP - 2003 Sep TI - Abundant expression of spliced HDM2 in Hodgkin lymphoma cells does not interfere with p14(ARF) and p53 binding. PG - 1587-96 AB - Recently, comparative genomic hybridization (CGH)- and fluorescence in situ hybridization (FISH)-analyses of native Hodgkin and Reed-Sternberg (H&RS) cells extracted from Hodgkin lymphoma (HL) revealed a recurrent amplification of the HDM2 locus on chromosome 12. HDM2 is known to target, inactivate and to degrade p53. Wild type (wt) p53 protein is detected in high levels in HL. Simultaneously, stabilized wt p53 and spliced hdm2 transcripts have been observed in different tumors. Therefore, we examined the expression and structure of HDM2 in HL cell lines and possible effects on components of the p53 pathway. DNA integrity and induction potential of p53 was verified by DNA sequencing and detection of potential effector proteins (p21(WAF/CIP), HDM2) using immunofluorescence, respectively. All HL cell lines show an overexpression of HDM2 protein. Furthermore, several different spliced hdm2 transcripts (mdm-sv) including five new variants lacking a functional p53 binding site were characterized. If expressed, corresponding proteins were shown to be not restricted to the nucleus. Co-localization of the potential binding partners HDM2/p14(ARF) and HDM2/p53 was found in HL cell lines. We suggest that HDM2-sv have no significant disturbing influence on the interaction of these proteins. FAU - Sturzenhofecker, Benjamin AU - Sturzenhofecker B AD - Department of Haematologie and Oncology, Georg August University, Goettingen 37075, Germany. b.stuerzen@med.uni-goettingen.de FAU - Schlott, Thilo AU - Schlott T FAU - Quentin, Thomas AU - Quentin T FAU - Kube, Dieter AU - Kube D FAU - Jung, Wolfram AU - Jung W FAU - Trumper, Lorenz AU - Trumper L LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Leuk Lymphoma JT - Leukemia & lymphoma JID - 9007422 RN - 0 (CDKN1A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p21) RN - 0 (Cyclins) RN - 0 (Neoplasm Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (RNA, Neoplasm) RN - 0 (Tumor Suppressor Protein p14ARF) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.3.2.27 (MDM2 protein, human) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) SB - IM MH - *Alternative Splicing MH - Binding Sites MH - Cell Line, Tumor/metabolism MH - Cell Nucleus/metabolism MH - Cyclin-Dependent Kinase Inhibitor p21 MH - Cyclins/biosynthesis/genetics MH - DNA Methylation MH - Gene Expression Regulation, Neoplastic MH - Hodgkin Disease/*genetics/metabolism/pathology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Neoplasm Proteins/chemistry/genetics/*metabolism/pharmacology MH - *Nuclear Proteins MH - Polymerase Chain Reaction MH - Protein Binding MH - Proto-Oncogene Proteins/chemistry/genetics/*metabolism/pharmacology MH - Proto-Oncogene Proteins c-mdm2 MH - RNA, Messenger/metabolism MH - RNA, Neoplasm/metabolism MH - Reed-Sternberg Cells/metabolism MH - Sequence Deletion MH - Tumor Suppressor Protein p14ARF/antagonists & inhibitors/*metabolism MH - Tumor Suppressor Protein p53/antagonists & inhibitors/*metabolism EDAT- 2003/10/21 05:00 MHDA- 2004/03/24 05:00 CRDT- 2003/10/21 05:00 PHST- 2003/10/21 05:00 [pubmed] PHST- 2004/03/24 05:00 [medline] PHST- 2003/10/21 05:00 [entrez] AID - 10.3109/10428190309178783 [doi] PST - ppublish SO - Leuk Lymphoma. 2003 Sep;44(9):1587-96. doi: 10.3109/10428190309178783.