title: The biphasic role of NF-kappaB in progression and chemoresistance of ovarian cancer.
abstract: OBJECTIVE
  NF-κB is a transcription factor known to promote tumorigenesis. However, NF-κB is also known to be proapoptotic and may potentially function as a tumor suppressor, although such a functional role has not been extensively investigated in human cancer.
  
  
  METHODS
  A dominant-negative mutant of IκBα with mutations at S32A and S36A was used to inhibit the function of NF-κB in ovarian cancer cell lines. The transcription ability, tumorigenesis, apoptosis, and drug sensitivity were examined in derivative cell lines in comparison with parental cells. We also analyzed the association of nuclear expression of NF-κB p65 with patient survival in an ovarian cancer tissue array.
  
  
  RESULTS
  We show that NF-κB functions as a tumor suppressor in four ovarian cancer cell lines, but it functions as an oncogene in their aggressive chemoresistant isogenic variants. NF-κB can exert its proapoptotic or antiapoptotic effect by activating or repressing mitogen-activated protein kinase (MAPK) phosphorylation in parental or aggressive chemoresistant variant cell lines. We also show that the nuclear accumulation of p65 in epithelial cancer tissue is associated with a good response to chemotherapy and can predict longer overall survival for patients with ovarian cancer.
  
  
  CONCLUSIONS
  Our data provide strong evidence that NF-κB can function as a biphasic regulator, either suppressing or enhancing ovarian cancer growth through the regulation of MAPK and cellular apoptosis.
authors.affiliation: Cancer Research Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Rosen
authors.forename: Xi
authors.initials: X
authors.lastname: Cheng
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Chang
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Liu
authors.forename: Fengxia
authors.initials: F
authors.lastname: Xue
authors.forename: Imelda
authors.initials: I
authors.lastname: Mercado-Uribe
authors.forename: Paul
authors.initials: P
authors.lastname: Chiao
authors.forename: Xiang
authors.initials: X
authors.lastname: Du
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D016190:Carboplatin; D020928:Mitogen-Activated Protein Kinases; D017239:Paclitaxel