Gene expression profile by blocking the SYT-SSX fusion gene in synovial sarcoma cells. Identification of XRCC4 as a putative SYT-SSX target gene.
Increasing evidence suggests that the SYT-SSX fusion gene plays an important role in synovial sarcoma development and progression. However, very little is known about the downstream targets of SYT-SSX. In this study, we used antisense oligonucleotides to block the expression of the SYT-SSX fusion gene in synovial sarcoma cells. By comparing SYT-SSX inhibited cells with noninhibited cells, the gene expression profile was analysed using cDNA microarray and established by real-time PCR. Herewith, using a filter containing 1176 cancer-relevant genes, we found that the DNA repair gene XRCC4 and the DNA mismatch repair gene MSH2 were downregulated, whereas the gene encoding for the serine/threonine protein kinase PRK (also known as CNK), and the macrophage inhibitory cytokine MICI (also known as PLAB) were upregulated after the inhibition of SYT-SSX. In comparison, expression of the XRCC4 gene was undergoing the strongest alteration. Consistently, the protein expression of XRCC4 was found to be decreased after SYT-SSX inhibition, whereas there were no detectable changes for the other gene products. Our study provides some clues to elucidate the signaling pathways of the SYT-SSX fusion gene, as well as it demonstrates a valuable model system for search for other SYT-SSX targets.
Department of Oncology and Pathology, CCK R8:04, Karolinska Hospital, SE-171 76, Stockholm, Sweden.
Yuntao
Y
Xie
Maria
M
Törnkvist
Yan
Y
Aalto
Gunnar
G
Nilsson
Leonard
L
Girnita
Bálint
B
Nagy
Sakari
S
Knuutila
Olle
O
Larsson
D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051718:MutS Homolog 2 Protein; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000378:metabolism*; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C116512:SYT-SSX fusion protein; C101467:XRCC4 protein, human; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein