PMID- 15307134
OWN - NLM
STAT- MEDLINE
DCOM- 20041012
LR  - 20061115
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 204
IP  - 1
DP  - 2004 Sep
TI  - Inverse correlation of secreted frizzled-related protein 4 and beta-catenin 
      expression in endometrial stromal sarcomas.
PG  - 19-27
AB  - 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.
CI  - Copyright 2004 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Hrzenjak, Andelko
AU  - Hrzenjak A
AD  - Department of Pathology, Medical University, Graz, Austria. 
      andelko.hrzenjak@klinikum-graz.at
FAU - Tippl, Michaela
AU  - Tippl M
FAU - Kremser, Marie-Luise
AU  - Kremser ML
FAU - Strohmeier, Bettina
AU  - Strohmeier B
FAU - Guelly, Christian
AU  - Guelly C
FAU - Neumeister, Doris
AU  - Neumeister D
FAU - Lax, Sigurd
AU  - Lax S
FAU - Moinfar, Farid
AU  - Moinfar F
FAU - Tabrizi, Ali Dastranj
AU  - Tabrizi AD
FAU - Isadi-Moud, Narges
AU  - Isadi-Moud N
FAU - Zatloukal, Kurt
AU  - Zatloukal K
FAU - Denk, Helmut
AU  - Denk H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Cytoskeletal Proteins/genetics/*metabolism
MH  - DNA, Neoplasm/genetics
MH  - Endometrial Neoplasms/genetics/*metabolism/pathology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - In Situ Hybridization
MH  - Neoplasm Proteins/genetics/*metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Proteins/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sarcoma/genetics/*metabolism/pathology
MH  - Trans-Activators/genetics/*metabolism
MH  - beta Catenin
EDAT- 2004/08/13 05:00
MHDA- 2004/10/13 09:00
CRDT- 2004/08/13 05:00
PHST- 2004/08/13 05:00 [pubmed]
PHST- 2004/10/13 09:00 [medline]
PHST- 2004/08/13 05:00 [entrez]
AID - 10.1002/path.1616 [doi]
PST - ppublish
SO  - J Pathol. 2004 Sep;204(1):19-27. doi: 10.1002/path.1616.