Skip Navigation


Carcinogenesis Advance Access originally published online on November 20, 2008
Carcinogenesis 2009 30(1):131-140; doi:10.1093/carcin/bgn230
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
30/1/131    most recent
bgn230v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Liao, X.
Right arrow Articles by Cheung, A. N.Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liao, X.
Right arrow Articles by Cheung, A. N.Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation

Xiaoyun Liao, Michelle K.Y. Siu, Christy W.H. Au, Esther S.Y. Wong, Hoi Yan Chan, Philip P.C. Ip, Hextan Y.S. Ngan1 and Annie N.Y. Cheung*

Department of Pathology
1 Department of Obstetrics and Gynecology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China

* To whom correspondence should be addressed. Tel: +852 2855 4876; Fax: +852 2872 5197; Email: anycheun{at}hkucc.hku.hk

Aberrant activation of hedgehog (HH) pathway has been implicated in the development of human malignancies. This study aimed at investigating the role of HH molecules in human ovarian carcinogenesis. The expression profiles of HH molecules were examined in ovarian tumor samples and ovarian cancer cell lines and the in vitro effects of HH molecules on cell proliferation, apoptosis, migration, invasion and cell differentiation as well as related downstream target genes were assessed. Overexpression of Patched and Gli1 protein in ovarian cancers correlated with poor survival of the patients (P = 0.008; P = 0.004). Significantly elevated expression of Sonic hedgehog messenger RNA was observed in ovarian cancers compared with normal tissues and benign ovarian tumors and such differential expression was specific to histological types (P < 0.05). Ectopic Gli1 overexpression in ovarian cancer cells conferred increased cell proliferation, cell mobility, invasiveness and change in differentiation in association with increased expression of E-cadherin, vimentin, Bcl-2, caspases as well as β1 integrin, membrane type 1 matrix metalloproteinase (MT1-MMP) and vascular endothelial growth factor (VEGF). Treatment with 3-keto-N-(aminoethyl-aminocaproyl-dihydrocinnamoyl)-cyclopamine induced cancer cell apoptosis, suppressed cell growth, mobility and invasiveness and induced cancer cell dedifferentiation with decreased expression of E-cadherin, cytokeratin 7, Snail, calretinin, vimentin, Bcl-2, caspases, β1 integrin, MT1-MMP and VEGF. Our data suggested that abnormal HH signaling activation plays important roles in the development and progression of ovarian cancers. Gli1 expression is an independent prognostic marker. Inhibition of the HH pathway molecules might be a valid therapeutic strategy for ovarian cancers.

Abbreviations: CI, confidence interval; FBS, fetal bovine serum; HH, hedgehog; KAAD, 3-keto-N-(aminoethyl-aminocaproyl-dihydrocinnamoyl); MT1-MMP, membrane type 1 matrix metalloproteinase; mRNA, messenger RNA; OSE, ovarian surface epithelium; PARP, poly(ADP-ribose) polymerase; PCR, polymerase chain reaction; RT, reverse transcription; SD, standard deviation; Shh, Sonic hedgehog; Smo, Smoothened; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay; VEGF, vascular endothelial growth factor

Received June 11, 2008; revised September 22, 2008; accepted September 24, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.