Expression of claudin7 is tightly associated with epithelial structures in synovial sarcomas and regulated by an Ets family transcription factor, ELF3.
Synovial sarcoma, a soft tissue sarcoma that develops in adults, is pathologically subclassified into monophasic spindle synovial sarcoma and biphasic synovial sarcoma with epithelial components. The molecular mechanism building the epithelial components in biphasic synovial sarcoma is totally unknown. Here we investigated claudins, critical molecules in the tight junction, in biphasic synovial sarcoma. Expression profiles of 21 claudins in 17 synovial sarcoma tumor samples, including 9 biphasic tumors, identified claudin4, claudin7, and claudin10 as biphasic tumor-related claudins, and immunohistochemical analyses demonstrated the localization of these claudins in the epithelial component in biphasic tumors, with claudin7 the most closely associated with the epithelial component. The mRNA expression and protein localization of claudin7 coincided with those of the ELF3, an epithelia-specific member of the Ets family of transcription factors. Luciferase reporter assays demonstrated that the presence of the Ets-binding site at -150 in the promoter region of the claudin7 gene was critical for the transcriptional activity, and gel shift and chromatin immunoprecipitation assays confirmed the binding of ELF3 to the Ets site at -150. Inhibition of ELF3 expression by small interfering RNA simultaneously down-regulated the mRNA expression of the claudin7 gene, and the introduction of ELF3 expression in claudin7-negative cell lines induced mRNA expression of the claudin7 gene. Therefore, the induction of claudin7 expression by ELF3 appears critical to the formation of the epithelial structures in biphasic synovial sarcoma.
Kohno
Yoshiki
Y
Institute for Frontier Medical Sciences, Kyoto University, 53 Kaweahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, USA.
Okamoto
Takeshi
T
Ishibe
Tatsuya
T
Nagayama
Satoshi
S
Shima
Yasuko
Y
Nishijo
Kohichi
K
Shibata
Kotaro R
KR
Fukiage
Kenichi
K
Otsuka
Seiji
S
Uejima
Daisuke
D
Araki
Nobuhito
N
Naka
Norifumi
N
Nakashima
Yasuaki
Y
Aoyama
Tomoki
T
Nakayama
Tomitaka
T
Nakamura
Takashi
T
Toguchida
Junya
J
D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D057167:Claudins; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism*
C473255:CLDN7 protein, human; D057167:Claudins; D017931:DNA Primers; D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors