The role of growth differentiation factor-9 (GDF-9) and its analog, GDF-9b/BMP-15, in human breast cancer.
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 beta-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).


CONCLUSIONS
Growth differentiation factor-9 family expressed in breast cancer has an inhibitory effect on the progression of human breast cancer.
Hanavadi
S
S
Metastasis and Angiogenesis Research Group, Wales College of Medicine, Cardiff University, Cardiff, UK.
Martin
T A
TA
Watkins
G
G
Mansel
R E
RE
Jiang
W G
WG
D055430:Bone Morphogenetic Protein 15; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D055429:Growth Differentiation Factor 9; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008207:Lymphatic Metastasis; D011379:Prognosis
C525901:BMP15 protein, human; D055430:Bone Morphogenetic Protein 15; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D036341:Intercellular Signaling Peptides and Proteins