| RRC ID |
44821
|
| 著者 |
Shinjo K, Yamashita Y, Yamamoto E, Akatsuka S, Uno N, Kamiya A, Niimi K, Sakaguchi Y, Nagasaka T, Takahashi T, Shibata K, Kajiyama H, Kikkawa F, Toyokuni S.
|
| タイトル |
Expression of chromobox homolog 7 (CBX7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation.
|
| ジャーナル |
Int J Cancer
|
| Abstract |
Ovarian cancer is the most lethal gynecologic malignancy, and clear cell adenocarcinoma of the ovary (OCCA), in particular, has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Chromobox (CBX) 7 is a polycomb repressive complex 1 component that prolongs the lifespan of normal human cells by downregulating the INK4a/ARF expression which promotes cell-cycle progression. However, recent reports studying the relationship between CBX7 expression and patient survival have differed regarding the tumor cell origins, and the precise role of CBX7 in human carcinomas remains obscure. In this study, we analyzed CBX7 expression by immunohistochemistry in 81 OCCA patients and evaluated its association with their clinical outcomes. Both the overall and progression-free survival rates of the CBX7-positive patients were significantly shorter than those of the CBX7-negative patients (p < 0.05). CBX7 knockdown experiments using two OCCA cell lines, TOV21G and KOC-7C, revealed that cell viability was significantly reduced compared to the control cells (p < 0.001). Expression microarray analysis revealed that apoptosis-related genes, particularly tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were significantly upregulated in CBX7 knockdown cells (p < 0.01). We further confirmed that CBX7 knockdown resulted in TRAIL-induced apoptosis in the OCCA cells. Thus, in this study, we showed for the first time that CBX7 was associated with a decreased OCCA prognosis. We also successfully demonstrated that the TRAIL pathway is a novel target for CBX7 expression modulation in these cells, and therapeutic agents utilizing the TRAIL pathway may be particularly effective for targeted OCCA therapy.
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| 巻・号 |
135(2)
|
| ページ |
308-18
|
| 公開日 |
2014-7-15
|
| DOI |
10.1002/ijc.28692
|
| PMID |
24375438
|
| MeSH |
Adenocarcinoma, Clear Cell / metabolism*
Adenocarcinoma, Clear Cell / mortality
Apoptosis / physiology*
Blotting, Western
Disease-Free Survival
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
In Situ Nick-End Labeling
Kaplan-Meier Estimate
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / mortality
Polycomb Repressive Complex 1 / biosynthesis*
Prognosis
Proportional Hazards Models
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / physiology
TNF-Related Apoptosis-Inducing Ligand / metabolism*
|
| IF |
5.145
|
| 引用数 |
35
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
