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Article: Increased expression of PITX2 transcription factor contributes to ovarian cancer progression

TitleIncreased expression of PITX2 transcription factor contributes to ovarian cancer progression
Authors
Issue Date2012
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2012, v. 7 n. 5, article no. e37076 How to Cite?
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. 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.
Persistent Identifierhttp://hdl.handle.net/10722/148750
ISSN
2013 Impact Factor: 3.534
2013 SCImago Journal Rankings: 1.724
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Wong Check She Charitable Foundation
Funding Information:

This study was supported by the Wong Check She Charitable Foundation. This support is from private donations, and no funder's website is available. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 

DC FieldValueLanguage
dc.contributor.authorFung, FKC-
dc.contributor.authorChan, DW-
dc.contributor.authorLiu, VWS-
dc.contributor.authorLeung, THY-
dc.contributor.authorCheung, ANY-
dc.contributor.authorNgan, HYS-
dc.date.accessioned2012-06-06T04:07:11Z-
dc.date.available2012-06-06T04:07:11Z-
dc.date.issued2012-
dc.identifier.citationPLoS One, 2012, v. 7 n. 5, article no. e37076-
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/148750-
dc.description.abstractBACKGROUND: 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.-
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS One-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleIncreased expression of PITX2 transcription factor contributes to ovarian cancer progressionen_US
dc.typeArticleen_US
dc.identifier.emailChan, DW: dwchan@hku.hk-
dc.identifier.emailLiu, VWS: vwsliu@hku.hk-
dc.identifier.emailLeung, THY: thyl@hku.hk-
dc.identifier.emailCheung, ANY: anycheun@hkucc.hku.hk-
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hk-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0037076-
dc.identifier.pmid22615897-
dc.identifier.pmcidPMC3352869-
dc.identifier.hkuros199852-
dc.identifier.volume7-
dc.identifier.issue5, article no. e37076-
dc.identifier.isiWOS:000305336300067-
dc.publisher.placeUnited States-

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