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Title: Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility

Abstract

Highlights: Black-Right-Pointing-Pointer We generated stable transduced HE4 overexpression and knockdown cells. Black-Right-Pointing-Pointer HE4 was associated with EOC cell adhesion and motility. Black-Right-Pointing-Pointer HE4 might have some effects on activation of EGFR-MAPK signaling pathway. Black-Right-Pointing-Pointer HE4 play an important role in EOC tumorigenicity. -- Abstract: Human epididymis protein 4 (HE4) is a novel and specific biomarker for epithelial ovarian cancer (EOC). We previously demonstrated that serum HE4 levels were significantly elevated in the majority of EOC patients but not in subjects with benign disease or healthy controls. However, the precise mechanism of HE4 protein function is unknown. In this study, we generated HE4-overexpressing SKOV3 cells and found that stably transduced cells promoted cell adhesion and migration. Knockdown of HE4 expression was achieved by stable transfection of SKOV3 cells with a construct encoding a short hairpin DNA directed against the HE4 gene. Correspondingly, the proliferation and spreading ability of HE4-expressed cells were inhibited by HE4 suppression. Mechanistically, impaired EGFR and Erk1/2 phosphorylation were observed in cells with HE4 knockdown. The phosphorylation was restored when the knockdown cells were cultured in conditioned medium containing HE4. Moreover, in vivo tumorigenicity showed that HE4 suppression markedly inhibited the growth of tumors. This suggests that expressionmore » of HE4 is associated with cancer cell adhesion, migration and tumor growth, which can be related to its effects on the EGFR-MAPK signaling pathway. Our results provide evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of HE4 in EOC progression. The role of HE4 as a target for gene-based therapy might be considered in future studies.« less

Authors:
 [1];  [2];  [3];  [4]; ; ;  [1];  [1];  [2]
  1. Department of Clinical Laboratory, Fudan University, Shanghai Cancer Center, Shanghai 200032 (China)
  2. (China)
  3. Department of Medicine, Brigham and Women's Hospital, MA 02115 (United States)
  4. (United States)
Publication Date:
OSTI Identifier:
22207743
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 419; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL MARKERS; CELL PROLIFERATION; DNA; GENES; HUMAN POPULATIONS; IN VIVO; INHIBITION; NEOPLASMS; PHOSPHORYLATION; PROTEINS; RNA; THERAPY

Citation Formats

Lu, Renquan, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, Sun, Xinghui, Department of Medicine, Harvard Medical School, MA 02115, Xiao, Ran, Zhou, Lei, Gao, Xiang, Guo, Lin, E-mail: guolin500@hotmail.com, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032. Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.02.008.
Lu, Renquan, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, Sun, Xinghui, Department of Medicine, Harvard Medical School, MA 02115, Xiao, Ran, Zhou, Lei, Gao, Xiang, Guo, Lin, E-mail: guolin500@hotmail.com, & Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032. Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. United States. doi:10.1016/J.BBRC.2012.02.008.
Lu, Renquan, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, Sun, Xinghui, Department of Medicine, Harvard Medical School, MA 02115, Xiao, Ran, Zhou, Lei, Gao, Xiang, Guo, Lin, E-mail: guolin500@hotmail.com, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032. Fri . "Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility". United States. doi:10.1016/J.BBRC.2012.02.008.
@article{osti_22207743,
title = {Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility},
author = {Lu, Renquan and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 and Sun, Xinghui and Department of Medicine, Harvard Medical School, MA 02115 and Xiao, Ran and Zhou, Lei and Gao, Xiang and Guo, Lin, E-mail: guolin500@hotmail.com and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032},
abstractNote = {Highlights: Black-Right-Pointing-Pointer We generated stable transduced HE4 overexpression and knockdown cells. Black-Right-Pointing-Pointer HE4 was associated with EOC cell adhesion and motility. Black-Right-Pointing-Pointer HE4 might have some effects on activation of EGFR-MAPK signaling pathway. Black-Right-Pointing-Pointer HE4 play an important role in EOC tumorigenicity. -- Abstract: Human epididymis protein 4 (HE4) is a novel and specific biomarker for epithelial ovarian cancer (EOC). We previously demonstrated that serum HE4 levels were significantly elevated in the majority of EOC patients but not in subjects with benign disease or healthy controls. However, the precise mechanism of HE4 protein function is unknown. In this study, we generated HE4-overexpressing SKOV3 cells and found that stably transduced cells promoted cell adhesion and migration. Knockdown of HE4 expression was achieved by stable transfection of SKOV3 cells with a construct encoding a short hairpin DNA directed against the HE4 gene. Correspondingly, the proliferation and spreading ability of HE4-expressed cells were inhibited by HE4 suppression. Mechanistically, impaired EGFR and Erk1/2 phosphorylation were observed in cells with HE4 knockdown. The phosphorylation was restored when the knockdown cells were cultured in conditioned medium containing HE4. Moreover, in vivo tumorigenicity showed that HE4 suppression markedly inhibited the growth of tumors. This suggests that expression of HE4 is associated with cancer cell adhesion, migration and tumor growth, which can be related to its effects on the EGFR-MAPK signaling pathway. Our results provide evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of HE4 in EOC progression. The role of HE4 as a target for gene-based therapy might be considered in future studies.},
doi = {10.1016/J.BBRC.2012.02.008},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 419,
place = {United States},
year = {Fri Mar 09 00:00:00 EST 2012},
month = {Fri Mar 09 00:00:00 EST 2012}
}
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