Journal Article

Epigenetic inactivation of the secreted frizzled-related protein-5 (<i>SFRP5</i>) gene in human breast cancer is associated with unfavorable prognosis

Jürgen Veeck, Cordelia Geisler, Erik Noetzel, Sevim Alkaya, Arndt Hartmann, Ruth Knüchel and Edgar Dahl

in Carcinogenesis

Volume 29, issue 5, pages 991-998
Published in print May 2008 | ISSN: 0143-3334
Published online March 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn076
Epigenetic inactivation of the secreted frizzled-related protein-5 (SFRP5) gene in human breast cancer is associated with unfavorable prognosis

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Disruption of the Wnt pathway is thought to be crucial in the development of human cancer. Pathway inhibitory members of the secreted frizzled-related protein (SFRP) family were found to be downregulated due to epigenetic inactivation in various malignancies. To date, only SFRP1 has been studied in human breast cancer and we questioned whether other SFRP genes may be implicated in the pathogenesis of this disease as well. An initial real-time polymerase chain reaction analysis of SFRP5 expression in normal human tissues (n = 9) revealed weak expression in most tissues, including breast. Malignant mammary cell lines showed further SFRP5 expression loss in five of six cases. Consistently, in matched pairs of primary breast tumor/normal breast tissue, this downregulation (>5-fold) could be confirmed (n = 8/13; 62%). We identified promoter methylation as the predominant mechanism of SFRP5 gene silencing since SFRP5 promoter methylation correlated significantly with loss of SFRP5 expression in cell lines (P = 0.040) and primary tumors (P = 0.003). Moreover, cancerous cell lines re-expressed SFRP5 messenger RNA following treatment with DNA-demethylating drugs. Of 168 primary breast carcinomas, 73% harbored a methylated SFRP5 promoter, whereas 27% were unaffected by epigenetic alteration. Most interestingly, SFRP5 methylation was associated with reduced overall survival (OS) (P = 0.045) and was an independent risk factor affecting OS in a multivariate Cox proportional hazard model (hazard ratio): 4.55; 95% confidence interval: 1.01–20.56; P = 0.049). In conclusion, SFRP5 is a target of epigenetic inactivation in human breast cancer, supporting the hypothesis of its role as tumor suppressor gene. SFRP5 methylation may be a novel DNA-based biomarker potentially useful in clinical breast cancer management.

Journal Article.  5935 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.