title: Inhibition of nuclear factor-kappa B enhances the tumor growth of ovarian cancer cell line derived from a low-grade papillary serous carcinoma in p53-independent pathway.
abstract: NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer.
  
  
  
  The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells.
  
  
  
  Western blot analysis indicated increased expression of the anti-apoptotic proteins Bcl-xL and reduced expression of the pro-apoptotic proteins Bax, Bad, and Bid in HOC-7/IĸBαM cell. Further investigations validate this conclusion in KRAS wildtype cell line SKOV3. Interesting, NF-kB can exert its pro-apoptotic effect by activating mitogen-activated protein kinase (MAPK) phosphorylation in SKOV3 ovarian cancer cell, whereas opposite changes detected in p-MEK in HOC-7 ovarian cancer cell, the same as some chemoresistant ovarian cancer cell lines. In vivo animal assay performed on BALB/athymic mice showed that injection of HOC-7 induced subcutaneous tumor growth, which was completely regressed within 7 weeks. In comparison, HOC-7/IĸBαM cells caused sustained tumor growth and abrogated tumor regression, suggesting that knock-down of NF-kB by IĸBαM promoted sustained tumor growth and delayed tumor regression in HOC-7 cells.
  
  
  
  Our results demonstrated that NF-kB may function as a tumor suppressor by facilitating regression of low grade ovarian serous carcinoma through activating pro-apoptotic pathways.
authors.affiliation: Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.|Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.affiliation: West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Bai
authors.affiliation: Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Shunping
authors.initials: S
authors.lastname: Gui
authors.affiliation: Department of Biochemistry and Molecular Biology, George Washington University, Washington, D.C., USA.
authors.forename: Tri M Bui
authors.initials: TM
authors.lastname: Nyuyen
authors.affiliation: Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Imelda
authors.initials: I
authors.lastname: Mercado-Uribe
authors.affiliation: Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Qintong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang, 82002, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chang
authors.affiliation: Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. wanghe_cd@126.com.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. 19811454@qq.com.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D000072000:NF-KappaB Inhibitor alpha
keywords: IkBαM; NF-kB; Ovarian cancer; Pro-apoptosis; Tumor suppressor