title: Increased expression of PITX2 transcription factor contributes to ovarian cancer progression.
abstract: BACKGROUND
  Paired-like homeodomain 2 (PITX2) is a bicoid homeodomain transcription factor which plays an essential role in maintaining embryonic left-right asymmetry during vertebrate embryogenesis. However, emerging evidence suggests that the aberrant upregulation of PITX2 may be associated with tumor progression, yet the functional role that PITX2 plays in tumorigenesis remains unknown.
  
  
  RESULTS
  Using real-time quantitative RT-PCR (Q-PCR), Western blot and immunohistochemical (IHC) analyses, we demonstrated that PITX2 was frequently overexpressed in ovarian cancer samples and cell lines. Clinicopathological correlation showed that the upregulated PITX2 was significantly associated with high-grade (P = 0.023) and clear cell subtype (P = 0.011) using Q-PCR and high-grade (P<0.001) ovarian cancer by IHC analysis. Functionally, enforced expression of PITX2 could promote ovarian cancer cell proliferation, anchorage-independent growth ability, migration/invasion and tumor growth in xenograft model mice. Moreover, enforced expression of PITX2 elevated the cell cycle regulatory proteins such as Cyclin-D1 and C-myc. Conversely, RNAi mediated knockdown of PITX2 in PITX2-high expressing ovarian cancer cells had the opposite effect.
  
  
  CONCLUSIONS
  Our findings suggest that the increased expression PITX2 is involved in ovarian cancer progression through promoting cell growth and cell migration/invasion. Thus, targeting PITX2 may serve as a potential therapeutic modality in the management of high-grade ovarian tumor.
authors.affiliation: Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Frederic K C
authors.initials: FK
authors.lastname: Fung
authors.forename: David W
authors.initials: DW
authors.lastname: Chan
authors.forename: Vincent W S
authors.initials: VW
authors.lastname: Liu
authors.forename: Thomas H Y
authors.initials: TH
authors.lastname: Leung
authors.forename: Annie N Y
authors.initials: AN
authors.lastname: Cheung
authors.forename: Hextan Y S
authors.initials: HY
authors.lastname: Ngan
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000097577:Homeobox Protein PITX2
chemical_list: D019938:Cyclin D1; D018398:Homeodomain Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D000097577:Homeobox Protein PITX2; C530105:Ccnd1 protein, mouse