Natural endogenous antiangiogenic molecule deficient in breast cancer

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Articles by Cai, J.
Articles by Boulton, M.
Clinical Cancer Research Vol. 12, 3510-3517, June 1, 2006
© 2006 American Association for Cancer Research
Cancer Therapy: Preclinical

Decreased Pigment Epithelium–Derived Factor Expression in Human Breast Cancer Progression

Jun Cai1, Christian Parr2, Gareth Watkins2, Wen G. Jiang2 and Mike Boulton3
Authors' Affiliations: 1 Cell and Molecular Biology Group, School of Optometry and Vision Sciences; 2 Metastasis and Angiogenesis Research Group, Department of Surgery, Wales College of Medicine, Cardiff University, Cardiff, United Kingdom; and 3 Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, Galveston, Texas

Requests for reprints: Mike Boulton, Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1106. Phone: 409-747-5413; Fax: 409-747-5402; E-mail: boultonm@utmb.edu.

Purpose: The aim of this study was to correlate the expression of pigment epithelium–derived factor (PEDF), a potent endogenous antiangiogenic molecule, with severity and prognosis in breast cancer.

Experimental Design: To investigate the gene expression profile of PEDF in human breast cancer in relation to a patient's clinical variables, we examined human breast cancer tissue (n = 119), background breast tissue (n = 33), and a range of cell lines for mRNA and protein levels of PEDF by using reverse transcription PCR, real-time quantitative PCR, immunohistochemistry, and ELISA.

Results: By using reverse transcription PCR, real-time quantitative PCR, immunohistochemistry, and ELISA, PEDF expression was found to be dramatically decreased in breast cancer. An overall outlook for the patients inversely correlated with PEDF mRNA levels. Exogenous PEDF inhibits endothelial tubule formation induced by breast cancer cell–conditioned medium, in vitro.

Conclusion: These observations collectively support the hypothesis that a lack of PEDF expression is a potent factor for the enhancement of tumor growth and angiogenesis in breast cancer.