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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...

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Autores principales: Fung, Frederic K. C., Chan, David W., Liu, Vincent W. S., Leung, Thomas H. Y., Cheung, Annie N. Y., Ngan, Hextan Y. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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.
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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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