PloS one, 2012-05, Vol.7 (5), p.e37076-e37076
2012
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- Autor(en) / Beteiligte
- Titel
- Increased expression of PITX2 transcription factor contributes to ovarian cancer progression
- Ist Teil von
- PloS one, 2012-05, Vol.7 (5), p.e37076-e37076
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0037076Titel-ID: cdi_plos_journals_1344321346
- Format
- –
- Schlagworte
- Aberration, Analysis, Animals, beta Catenin - genetics, beta Catenin - metabolism, Biology, c-Myc protein, Cancer, Cell cycle, Cell Cycle - genetics, Cell growth, Cell Growth Processes - physiology, Cell Line, Tumor, Cell migration, Cell Movement - genetics, Cell proliferation, Cyclin D1 - genetics, Cyclin D1 - metabolism, Disease Progression, Embryogenesis, Embryonic growth stage, Epidemiology, Female, Gene expression, Gene Expression Regulation, Neoplastic, Genes, myc - genetics, Gynecology, Health aspects, Homeobox, Homeobox Protein PITX2, Homeodomain Proteins - biosynthesis, Homeodomain Proteins - genetics, Homeodomain Proteins - metabolism, Humans, Leukocyte migration, Medical prognosis, Medicine, Mice, Molecular biology, Morphogenesis, Myc protein, Neoplasm Invasiveness, Obstetrics, Ovarian cancer, Ovarian carcinoma, Ovarian Neoplasms - genetics, Ovarian Neoplasms - metabolism, Ovarian Neoplasms - pathology, Pathology, Plasmids, Polymerase chain reaction, Proteins, Regulatory proteins, Review boards, RNA-mediated interference, Thyroid cancer, Transcription factors, Transcription Factors - biosynthesis, Transcription Factors - genetics, Transcription Factors - metabolism, Tumor cell lines, Tumorigenesis, Tumors, Up-Regulation, Wnt Proteins - genetics, Wnt Proteins - metabolism, Xenografts