Upregulation of CD9 in ovarian cancer is related to the induction of TNF-alpha gene expression and constitutive NF-kappaB activation = 난소암에서 CD9의 과발현은 TNF-alpha 유전자 발현의 유도와 NF-kappaB의 지속적 활성화와 관련

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Title
Upregulation of CD9 in ovarian cancer is related to the induction of TNF-alpha gene expression and constitutive NF-kappaB activation = 난소암에서 CD9의 과발현은 TNF-alpha 유전자 발현의 유도와 NF-kappaB의 지속적 활성화와 관련
Author(s)
J R Hwang; K Jo; Y Lee; B J Sung; Young Woo Park; J H Lee
Bibliographic Citation
Carcinogenesis, vol. 33, no. 1, pp. 77-83
Publication Year
2012
Abstract
Ovarian cancer is a gynecological cancer with a high death rate. We utilized global gene expression profiles of ovarian carcinomas obtained by complementary DNA (cDNA) microarray to identify ovarian cancer-specific proteins. CD9 was upregulated in ovarian carcinomas, and overexpression of the CD9 protein was detected in ovarian carcinomas by immunohistochemistry. CD9 was also overexpressed in several cancer cell lines, including ovarian cancer cells. In order to elucidate the biological significance of highly expressed CD9 in cancer cells, functional studies of CD9 were performed by ectopic expression, knockdown of CD9 using small interfering RNA (siRNA) and blockage of CD9 activity using the CD9-specific monoclonal antibody ALB6. Ectopic CD9 induced cell survival. In order to identify signaling pathways related to CD9, the gene expressions of CD9/SKOV3 cells were analyzed by cDNA microarray. Among the many upregulated genes, tumor necrosis factor (TNF)-α was induced in CD9/SKOV3 cells. The effect of overexpressed CD9 on the downstream signaling events of TNF-α was further investigated. In CD9/SKOV3 cells, the nuclear factor-kappaB (NF-κB)-signaling pathway was constitutively activated. Knockdown of CD9 by siRNA and blockage of CD9 activity by ALB6 in ovarian cancer cells demonstrated that constitutive activation of NF-κB is CD9 dependent and that CD9 is involved in anti-apoptosis. A CD9 functional study was performed in an ovarian cancer-xenograft mouse by injecting ALB6 into the peritoneum. ALB6 resulted in reduced tumor weight compared with that of control IgG 1. Collectively, these results demonstrate that CD9 functions as an oncogene and represents a target for the development of cancer-specific therapeutics.
ISSN
0143-3334
Publisher
Oxford Univ Press
DOI
http://dx.doi.org/10.1093/carcin/bgr257
Type
Article
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1. Journal Articles > Journal Articles
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