Bone morphogenetic proteins 1 to 7 in human breast cancer, expression pattern and clinical/prognostic relevance
Simon R. Davies, Gareth Watkins, Anthony Douglas-Jones, Robert E. Mansel and Wen G Jiang
Background and aims: Bone morphogenetic proteins (BMPs) have a diverse role and they act in a time, concentration and cell type specific manner. They regulate cellular motility and the cells ability to invade. Recently, BMP molecules have further been shown to have an impact on the biological behaviour of breast cancer cells. In this study, we looked, for the first time, at the expression of a panel of BMPs in breast carcinomas.
Method: Fresh frozen primary human breast cancer tissues (n = 120) and non-neoplastic mammary tissues (n = 32) were used. The distribution and location of BMPs was assessed using immunohistochemical methods and the transcript levels of BMPs (BMP-1, -2, -3, -4, -5, -6, and -7) were determined using quantitative RT-PCR. The results were analysed against the clinical, pathological and follow-up (10 years) data.
Results: BMP-2 and BMP-7 exhibited contrasting patterns of expression in normal and tumour tissues, wherein BMP-2 transcript level was lower and BMP- 7 was higher in breast tumours than normal tissues. BMP-2 transcript was also significantly lower in tumours from patients with a moderate and poor prognosis than from those with a good prognosis (p = 0.04). BMP-2 and BMP-7 also showed a significant difference between node positive and node negative tumours (p = 0.033 and p = 0.031 respectively). BMPs 1, 3, 4, 5 and 6 showed an inconsistent variation in transcript levels within the cancer subgroups with no statistically significant results.
Conclusion: This study has demonstrated a differential pattern of expression of BMP molecules in breast cancer and reveals a potential prognostic value of BMP-2 and BMP-7 for patients. The findings also suggest that these BMPs may be potential therapeutic targets.
Keywords: Bone morphogenetic proteins, BMP, breast cancer