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AuthorBucur, Alexandra Julianadc.contributor.author
Date of accession2016-03-14T13:40:09Zdc.date.accessioned
Available in OPARU since2016-03-14T13:40:09Zdc.date.available
Year of creation2005dc.date.created
AbstractMediastinal (thymic) B-cell lymphoma (MBL) is a locally highly aggressive tumor and a distinct subclass of diffuse large B-cell lymphoma. MBL exhibits several characteristic genetic abnormalities; including frequent gains of chromosome 9p and distinct high-level amplifications, with the consensus region 9p24, including the Janus Kinase 2 (Jak2) locus. Janus Kinases (Jaks) and their downstream targets, Signal Transducers and Activators of Transcription (STAT proteins) trigger via activation the cytokine induced signal. In MedB-1, a cell line established from a mediastinal B-cell lymphoma, was found about the double dose of Jak2 DNA compared to autologuos fibroblasts, Jak2 m-RNA expression in MedB-1 cells was also higher than in resting peripheral B cells. The results indicated that Jak2 was not overexpressed at the protein level but highly phosphorylated in MedB-1 cells, its protein turn-over being delayed. STAT5 proteins, downstream partner of Jak2 were highly expressed and phosphorylated at the protein level. MedB-1 also expressed high level of Cyclin D1 one of STAT5 target genes important in cell-cycle regulation. SOCS-1(suppressor of cytokine signaling-1) it is one of the most intensively studied Jak2 negative regulators. The central finding in MedB-1 cells is a biallelic mutation in the SOCS-1 gene, which abrogates SOCS box function of the protein. Ectopic expression of wild-type (wt) SOCS-1 in MedB-1 leads to growth arrest and dramatic reduction of phospho-Jak2 and its downstream partner. Ultimately, the target gene cyclin D1 is repressed in transfectants while Rb1, which is silenced in MedB-1, is induced. In conclusion, in MedB-1, the action of phospho-Jak2 is sustained due to defective SOCS-1.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (Fassung vom 03.05.2003)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v1dc.rights.uri
KeywordJanus Kinase 2dc.subject
KeywordMediastinal B-cell lymphoma (MBL)dc.subject
KeywordSignal transducers and activators of transcription (STAT)dc.subject
KeywordSOCS-1 mutationsdc.subject
KeywordSuppressor of cytokine signalling (SOCS-1)dc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
TitleConstitutive activation of Jak2/STAT5-signalling pathway in MedB-1 cells due to deficient SOCS-1dc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-573dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-54068dc.identifier.urn
GNDB-Zell-Lymphomdc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
Date of activation2005-12-13T14:59:39Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionZ: J-H 10.921 ; W: W-H 8.868uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS-ID5406uulm.vtsID
CategoryPublikationenuulm.category


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