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Published in: Annals of Surgical Oncology 7/2007

01-07-2007 | Laboratory Research

The Role of Growth Differentiation Factor-9 (GDF-9) and Its Analog, GDF-9b/BMP-15, in Human Breast Cancer

Authors: S. Hanavadi, MS, FRCS, T. A. Martin, PhD, G. Watkins, HND, R. E. Mansel, MS, FRCS, W. G. Jiang, MB BCh, MD

Published in: Annals of Surgical Oncology | Issue 7/2007

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Abstract

Background

There has been a recent surge of interest in the role of growth differentiation factors and other bone morphogenic proteins in the development and spread of cancer. In this study we have provided evidence that highlights the significance of growth and differentiation factor-9a (GDF-9a) and GDF-9b (bone morphogenic protein-15, BMP-15) in breast cancer development and progression.

Methods

Primary breast cancer samples (n = 109) and matched background tissues from same patients (n = 33) were processed for frozen section and RNA extraction. Frozen sections from matched tissues were immunostained with GDF-9a and GDF-9b antibodies. Staining intensity was analyzed by computer image analysis. RNA was reverse transcribed and quantified before analysis by quantitative polymerase chain reaction (Q-PCR). Results were expressed as number of transcripts (standardized by β-actin). The data were compared with the clinical outcome of the disease. The biological effects of the molecule were studied using in vitro assays after forced expression in breast cancer cells.

Results

Highly aggressive breast cancer cells did not express GDF-9a. On forced expression of GDF-9a, breast cancer cells became less invasive. These laboratory findings were analyzed against the clinical information. Primary breast cancer samples with good predicted prognosis had a significantly higher level of GDF-9a than in samples with poor predicted prognosis (P = .004). Patients who remained disease-free at the end of a 10-year follow-up had significantly higher levels of both GDF-9a and GDF-9b in their tissue than those with poor clinical outcome (P = .001 and .014, respectively).

Conclusion

Growth differentiation factor-9 family expressed in breast cancer has an inhibitory effect on the progression of human breast cancer.
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Metadata
Title
The Role of Growth Differentiation Factor-9 (GDF-9) and Its Analog, GDF-9b/BMP-15, in Human Breast Cancer
Authors
S. Hanavadi, MS, FRCS
T. A. Martin, PhD
G. Watkins, HND
R. E. Mansel, MS, FRCS
W. G. Jiang, MB BCh, MD
Publication date
01-07-2007
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 7/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-007-9397-5

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