Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hrzenjak, A; Tippl, M; Kremser, ML; Strohmeier, B; Guelly, C; Neumeister, D; Lax, S; Moinfar, F; Tabrizi, AD; Isadi-Moud, N; Zatloukal, K; Denk, H.
Inverse correlation of secreted frizzled-related protein 4 and beta-catenin expression in endometrial stromal sarcomas.
J PATHOL. 2004; 204(1): 19-27.
Doi: 10.1002/path.1616
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Hrzenjak Andelko
- Co-Autor*innen der Med Uni Graz
- Denk Helmut
- Gülly Christian
- Moinfar Farid
- Tippl Michaela
- Zatloukal Kurt
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- Abstract:
- Endometrial stromal sarcomas are rare uterine tumours. Whereas the histology and immunohistochemistry of these tumours are well documented, almost nothing is known about the molecular mechanisms involved in their pathogenesis. To characterize the genes altered in these malignancies, a genome-wide cDNA library was generated by suppression subtractive hybridization and a set of differentially expressed clones was isolated. These were then used to produce custom-spotted cDNA arrays. Genes deregulated in endometrial stromal sarcomas were identified by cDNA array hybridization and were confirmed by quantitative real-time PCR analyses and in situ hybridization. Following cDNA array analysis, more than 300 genes deregulated in endometrial stromal sarcoma were selected and sequenced. Among the most significantly deregulated genes were those of secreted frizzled-related proteins (SFRPs), in particular secreted frizzled-related protein 4 (SFRP4). SFRPs are putative modulators of the Wnt-signalling pathway and play a role in different cellular events including cell proliferation. Compared with normal endometrium, the expression of SFRP4 was decreased in both low-grade endometrial stromal sarcoma (ESS; n = 10) and undifferentiated endometrial sarcoma (UES; n = 4), being lower in the latter more aggressive form. These results were verified on paraffin wax-embedded tissue by quantitative real-time PCR analysis and in situ hybridization. Furthermore, the expression of beta-catenin, an important component of the Wnt-signalling pathway, was regulated in an opposite manner to SFRP4, being particularly increased in undifferentiated sarcomas. The activation of the Wnt-signalling pathway was additionally supported by the immunohistochemical demonstration that beta-catenin was translocated to the nucleus in UES. SFRP4 may therefore be a putative tumour suppressor involved in deregulation of the Wnt pathway and in the pathogenesis of ESS and UES.
- Find related publications in this database (using NLM MeSH Indexing)
- Cytoskeletal Proteins - genetics
- DNA, Neoplasm - genetics
- Endometrial Neoplasms - genetics
- Female - genetics
- Gene Expression Regulation, Neoplastic - genetics
- Humans - genetics
- In Situ Hybridization - genetics
- Neoplasm Proteins - genetics
- Oligonucleotide Array Sequence Analysis - genetics
- Proteins - genetics
- Reverse Transcriptase Polymerase Chain Reaction - genetics
- Sarcoma - genetics
- Trans-Activators - genetics
- beta Catenin - genetics
- Find related publications in this database (Keywords)
- endometrial stromal sarcoma
- QRT-PCR
- secreted frizzled-related proteins
- Wnt pathway
- beta-catenin