Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains and Activation of the Nuclear Factor κB Pathway and Is Associated with Poor Overall Survival
Ovarian cancer is a leading cause of cancer mortality in women. The aim of this study was to elucidate whether whey acidic protein (WAP) genes on chromosome 20q13.12, a region frequently amplified in this cancer, are expressed in serous carcinoma, the most common form of the disease. Herein, we rep...
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doaj-7fbbdb2b432a4154a7239cbd493201892020-11-24T23:32:02ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022010-02-0112216117210.1593/neo.91542Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains and Activation of the Nuclear Factor κB Pathway and Is Associated with Poor Overall SurvivalAdam Clauss0Vivian Ng1Joyce Liu2Huiying Piao3Moises Russo4Natalie Vena5Qing Sheng6Michelle S. Hirsch7Tomas Bonome8Ursula Matulonis9Azra H. Ligon10Michael J. Birrer11Ronny Drapkin12Dana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USADana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USADana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USADana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USADana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USADana-Farber Cancer Institute, Center for Molecular Oncologic Pathology, Boston, MA, USAHarvard Medical School, Boston, MA, USAHarvard Medical School, Boston, MA, USANational Institutes of Health, Molecular Mechanisms Section, Bethesda, MD, USADana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USAHarvard Medical School, Boston, MA, USAHarvard Medical School, Boston, MA, USADana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA, USA Ovarian cancer is a leading cause of cancer mortality in women. The aim of this study was to elucidate whether whey acidic protein (WAP) genes on chromosome 20q13.12, a region frequently amplified in this cancer, are expressed in serous carcinoma, the most common form of the disease. Herein, we report that a trio of WAP genes (HE4, SLPI, and Elafin) is overexpressed and secreted by serous ovarian carcinomas. To our knowledge, this is the first report linking Elafin to ovarian cancer. Fluorescence in situ hybridization analysis of primary tumors demonstrates genomic gains of the Elafin locus in a majority of cases. In addition, a combination of peptidomimetics, RNA interference, and chromatin immunoprecipitation experiments shows that Elafin expression can be transcriptionally upregulated by inflammatory cytokines through activation of the nuclear factor κB pathway. Importantly, using a clinically annotated tissue microarray composed of late-stage, high-grade serous ovarian carcinomas, we show that Elafin expression correlates with poor overall survival. These results, combined with our observation that Elafin is secreted by ovarian tumors and is minimally expressed in normal tissues, suggest that Elafin may serve as a determinant of poor survival in this disease. http://www.sciencedirect.com/science/article/pii/S1476558610800958 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Adam Clauss Vivian Ng Joyce Liu Huiying Piao Moises Russo Natalie Vena Qing Sheng Michelle S. Hirsch Tomas Bonome Ursula Matulonis Azra H. Ligon Michael J. Birrer Ronny Drapkin |
spellingShingle |
Adam Clauss Vivian Ng Joyce Liu Huiying Piao Moises Russo Natalie Vena Qing Sheng Michelle S. Hirsch Tomas Bonome Ursula Matulonis Azra H. Ligon Michael J. Birrer Ronny Drapkin Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains and Activation of the Nuclear Factor κB Pathway and Is Associated with Poor Overall Survival Neoplasia: An International Journal for Oncology Research |
author_facet |
Adam Clauss Vivian Ng Joyce Liu Huiying Piao Moises Russo Natalie Vena Qing Sheng Michelle S. Hirsch Tomas Bonome Ursula Matulonis Azra H. Ligon Michael J. Birrer Ronny Drapkin |
author_sort |
Adam Clauss |
title |
Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains and Activation of the Nuclear Factor κB Pathway and Is Associated with Poor Overall Survival |
title_short |
Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains and Activation of the Nuclear Factor κB Pathway and Is Associated with Poor Overall Survival |
title_full |
Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains and Activation of the Nuclear Factor κB Pathway and Is Associated with Poor Overall Survival |
title_fullStr |
Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains and Activation of the Nuclear Factor κB Pathway and Is Associated with Poor Overall Survival |
title_full_unstemmed |
Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains and Activation of the Nuclear Factor κB Pathway and Is Associated with Poor Overall Survival |
title_sort |
overexpression of elafin in ovarian carcinoma is driven by genomic gains and activation of the nuclear factor κb pathway and is associated with poor overall survival |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2010-02-01 |
description |
Ovarian cancer is a leading cause of cancer mortality in women. The aim of this study was to elucidate whether whey acidic protein (WAP) genes on chromosome 20q13.12, a region frequently amplified in this cancer, are expressed in serous carcinoma, the most common form of the disease. Herein, we report that a trio of WAP genes (HE4, SLPI, and Elafin) is overexpressed and secreted by serous ovarian carcinomas. To our knowledge, this is the first report linking Elafin to ovarian cancer. Fluorescence in situ hybridization analysis of primary tumors demonstrates genomic gains of the Elafin locus in a majority of cases. In addition, a combination of peptidomimetics, RNA interference, and chromatin immunoprecipitation experiments shows that Elafin expression can be transcriptionally upregulated by inflammatory cytokines through activation of the nuclear factor κB pathway. Importantly, using a clinically annotated tissue microarray composed of late-stage, high-grade serous ovarian carcinomas, we show that Elafin expression correlates with poor overall survival. These results, combined with our observation that Elafin is secreted by ovarian tumors and is minimally expressed in normal tissues, suggest that Elafin may serve as a determinant of poor survival in this disease.
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url |
http://www.sciencedirect.com/science/article/pii/S1476558610800958 |
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