Skip Navigation


Carcinogenesis Advance Access originally published online on September 16, 2008
Carcinogenesis 2009 30(1):114-121; doi:10.1093/carcin/bgn215
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
30/1/114    most recent
bgn215v1
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 arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Chan, Q. K.Y.
Right arrow Articles by Cheung, A. N.Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chan, Q. K.Y.
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

Tumor suppressor effect of follistatin-like 1 in ovarian and endometrial carcinogenesis—a differential expression and functional analysis

Queeny K.Y. Chan1, Hextan Y.S. Ngan2, Philip P.C. Ip1, Vincent W.S. Liu2, W.C. Xue1 and Annie N.Y. Cheung1,*

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

* To whom correspondence should be addressed. Tel: +86 852 2855 4876; Fax: +86 852 2872 5197; Email: anycheun{at}hkucc.hku.hk

Endometrial and ovarian cancers are the most common and the most lethal gynecologic malignancies worldwide, respectively. By performing differential expression analysis using annealing control primerTM-based reverse transcription (RT)–polymerase chain reaction (PCR) on pooled complementary DNA (cDNA) from 45 endometrial and 36 ovarian cancers and their non-tumor samples, reduced expression of the follistatin-like 1 (FSTL1) was identified. Downregulation of FSTL1 was further confirmed on individual samples and cell lines by quantitative real-time RT–PCR and western blotting. For in vitro functional study, full-length cDNA of FSTL1 was cloned and transiently transfected into the ovarian cancer cell line Ovca420 and endometrial cancer cell line AN3CA. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count demonstrated significantly slower proliferation rate. By terminal uridine deoxynucleotidyl transferase dUTP nick end labeling and flow cytometric analysis, higher apoptotic activity and a remarkable increase in sub-G1 cell population were observed in transfected cells, suggesting that FSTL1 induced apoptosis in cancer cells. Subsequent messenger RNA and protein expression analysis on downstream apoptotic molecules revealed upregulation and/or activation of FAS, FASLG, TRADD, Caspase-3, Caspase-7 and PARP by FSTL1 transfection, suggesting that FSTL1-induced apoptosis may be initiated mainly by FAS/FASLG death receptor–ligand binding. Cell migration and invasion assays demonstrated a remarkably lower cell migration and invasion capability in FSTL1-transfected cells in relation to downregulation of matrix metallopeptidase-2. Our findings suggested that a tumor suppressor role of FSTL1 may be important in ovarian and endometrial carcinogenesis.

Abbreviations: ACP, annealing control primer; cDNA, complementary DNA; EmCA, endometrial carcinoma; FSTL1, follistatin-like 1; MMP, matrix metallopeptidase; mRNA, messenger RNA; OvCA, ovarian carcinoma; PCR, polymerase chain reaction; RT, reverse transcription

Received May 5, 2008; revised September 6, 2008; accepted September 7, 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.