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Please use this identifier to cite or link to this item:
http://ntur.lib.ntu.edu.tw/handle/246246/64150
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| Title: | Transcription factor SOX-5 enhances nasopharyngeal carcinoma progression by down-regulating SPARC gene expression |
| Authors: | 林欽塘;Huang, D-Y;Lin, Y-T;Jan, P-S;Hwang, Y-C;Liang, S-T;Peng, Y;Huang, C-YF;Wu, H-C;Lin, C-T |
| Contributors: | 病理學科暨研究所 |
| Keywords: | nasopharyngeal carcinoma (NPC);NPC progression;NPC prognosis;SOX5;SPARC |
| Date: | 2008-03 |
| Issue Date: | 2008-02-27T09:22:55Z |
| Abstract: | Nasopharyngeal carcinoma (NPC) is prevalent in south-eastern Asia, and its tumourigenesis
is rather complex. The purpose of this research was to identify the pivotal genes that may be
altered during the early stage of NPC progression. Eleven genes were selected by comparative
microarray analysis of NPC versus normal nasomucosal cells. The expression of SPARC
(secreted protein, acidic, cysteine-rich) was statistically significantly down-regulated in NPC
cells. In exploring the mechanism underlying the decreased transcription of SPARC in NPC
cells, we found that the transcription factor SRY (sex-determining region Y)-box 5 (SOX-5)
is up-regulated in NPC cells. RNA interference of SOX-5 by short hairpin RNA (shRNA) in
NPC cells caused a dramatic increase in SPARC and chromosome immunoprecipitation
assay showed that SOX-5 can bind directly to the SPARC promoter, suggesting that
SOX-5 acts as a key transcriptional repressor of SPARC. We further demonstrated that
shRNA knockdown of SOX-5 suppressed the proliferation of NPC cells, as well as their
migratory ability, which was also observed when SPARC was over-expressed in NPC
cells. Alternatively, blocking SPARC with an antagonistic antibody reversed the effects
of SOX-5 knockdown. In 66 NPC patients, over-expression of SOX-5 in tumour cells
correlated clinically with poor survival. Our study suggests that SOX-5 transcriptionally
down-regulates SPARC expression and plays an important role in the regulation of NPC
progression. SOX-5 is a potential tumour marker for poor NPC prognosis. |
| Relation: | Journal of Pathology 2008; 214: 445–455 |
| Appears in Collections: | [病理學科暨研究所] 期刊論文
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