title: Cancerous inhibitor of protein phosphatase 2A is overexpressed in cervical cancer and upregulated by human papillomavirus 16 E7 oncoprotein.
abstract: OBJECTIVE
  Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein stabilizing c-Myc and promoting cell proliferation and transformation. Here we investigated the role of CIP2A in cervical cancer in vivo and in vitro.
  
  
  METHODS
  CIP2A expression was assessed in normal cervical, cervical intraepithelial neoplasia (CIN) I to III and cervical cancer tissues by immunohistochemistry and RT-PCR. Cell growth was explored by cell proliferation assay, colony formation assay and anchorage-independent growth in soft agar after inhibition of CIP2A by siRNA in HeLa, SiHa and Caski cells. Crosstalk of CIP2A and HPV16 E7 was investigated by immunohistochemistry in cervical cancer tissues and by real-time PCR and western blot analysis after HPV16 E7 inhibition by siRNA in SiHa cells.
  
  
  RESULTS
  CIP2A was transcribed in 73.3% of cervical cancer tissues (n=15) but not in normal cervical tissues (n=8). CIP2A protein was detected in 52.8% of cervical cancer (n=72) and 12.5% of CIN III tissues (n=24) but not in normal (n=15), CIN I (n=21) or CIN II samples (n=25). CIP2A protein level was positively associated with HPV16 E7 level in cervical cancer tissues. CIP2A expression was markedly reduced after E7 depletion. Moreover, CIP2A depletion reduced c-Myc protein level and impaired proliferation and growth of cervical cancer cells.
  
  
  CONCLUSIONS
  CIP2A is overexpressed in cervical cancer and promotes the malignant growth of cervical cancer cells. Its expression is upregulated by HPV16 E7. Therefore, CIP2A plays an important role in carcinogenesis of cervical cancer and shows promise for the diagnosis and treatment of cervical cancer.
authors.affiliation: Department of Microbiology and Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Xiang
authors.forename: Yizhe
authors.initials: Y
authors.lastname: Cheng
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jihui
authors.initials: J
authors.lastname: Jia
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhao
mesh_terms: D001324:Autoantigens / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D005260:Female; D016259:Genes, myc; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D050725:Papillomavirus E7 Proteins / Q000032:analysis / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; C059731:oncogene protein E7, Human papillomavirus type 16