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Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression
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 t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352869/ https://www.ncbi.nlm.nih.gov/pubmed/22615897 http://dx.doi.org/10.1371/journal.pone.0037076 |
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author | Fung, Frederic K. C. Chan, David W. Liu, Vincent W. S. Leung, Thomas H. Y. Cheung, Annie N. Y. Ngan, Hextan Y. S. |
author_facet | Fung, Frederic K. C. Chan, David W. Liu, Vincent W. S. Leung, Thomas H. Y. Cheung, Annie N. Y. Ngan, Hextan Y. S. |
author_sort | Fung, Frederic K. C. |
collection | PubMed |
description | 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. PRINCIPAL FINDINGS: 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. CONCLUSION: 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. |
format | Online Article Text |
id | pubmed-3352869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33528692012-05-21 Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression Fung, Frederic K. C. Chan, David W. Liu, Vincent W. S. Leung, Thomas H. Y. Cheung, Annie N. Y. Ngan, Hextan Y. S. PLoS One Research Article 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. PRINCIPAL FINDINGS: 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. CONCLUSION: 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. Public Library of Science 2012-05-15 /pmc/articles/PMC3352869/ /pubmed/22615897 http://dx.doi.org/10.1371/journal.pone.0037076 Text en Fung et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Fung, Frederic K. C. Chan, David W. Liu, Vincent W. S. Leung, Thomas H. Y. Cheung, Annie N. Y. Ngan, Hextan Y. S. Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression |
title | Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression |
title_full | Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression |
title_fullStr | Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression |
title_full_unstemmed | Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression |
title_short | Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression |
title_sort | increased expression of pitx2 transcription factor contributes to ovarian cancer progression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3352869/ https://www.ncbi.nlm.nih.gov/pubmed/22615897 http://dx.doi.org/10.1371/journal.pone.0037076 |
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