title: Molecular analysis of oncogenicity of the transcription factor, BRN3A, in cervical cancer cells.
abstract: OBJECTIVE
  The host cellular transcription factor, BRN3A, has been observed to play a vital role in cancer of the uterine cervix. BRN3A possesses multipartite functions, which include transcription of the genes of the high-risk HPVs and mediation of cellular changes in the host. In this study, we made an effort to decipher the regulation of BRN3A in cervical cancer cells by studying its interaction with different components of the cell.
  
  
  METHODS
  In cervical cancer cells, the endogenous HIPK2 was induced through cisplatin treatment, and then, its subsequent effect on BRN3A was primarily investigated through co-immunostaining and western blotting as HIPK2 has been observed to act as a co-repressor of Brn3a. The physical interaction of the two proteins was analyzed through co-immunoprecipitation. We resorted to chromatin immunoprecipitation in order to testify the autoregulatory pathway of BRN3A in cervical cancer cells. Interaction of BRN3A with cellular components, p73 and active form of JNK, was also studied through co-immunostaining.
  
  
  RESULTS
  We observed that BRN3A is independent of the regulative activity of HIPK2 and undergoes positive autoregulation in cervical cancer cells. Interestingly, during the study, it was revealed that BRN3A is unaffected by the treatment of cisplatin. Interaction of BRN3A with p73 and phosphorylated JNK in cervical cancer cells, observed in the present study, would help in understanding the molecular mechanism directed by BRN3A.
  
  
  CONCLUSIONS
  BRN3A possesses anti-apoptotic property, and considering the above results, it may be regarded as the key component in promoting tumorigenic growth in the uterine cervical cells.
authors.affiliation: Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Biswa Pratim
authors.initials: BP
authors.lastname: Das Purkayastha
authors.forename: Jagat Kumar
authors.initials: JK
authors.lastname: Roy
mesh_terms: D002352:Carrier Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology; D005260:Female; D006706:Homeostasis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D050819:Transcription Factor Brn-3A / Q000502:physiology*; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000502:physiology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C494188:POU4F1 protein, human; C000606460:TP73 protein, human; D050819:Transcription Factor Brn-3A; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D002945:Cisplatin