Bone morphogenetic protein 10 (BMP-10) inhibits growth of breast cancer cells and correlates with poor prognosis.

Abstract

Abstract Abstract #4068 Background: Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily and are known to be involved in the development of bone metastasis from solid tumours. Recent studies have shown that BMP-10 plays some critical roles during the fetal or postnatal development, particularly during the morphogenesis of heart. However, its role in cancer is largely unknown. The present study investigated the role of BMP-10 in breast cancer cells and pattern of expression in clinical breast cancers.
 Methods: The expression of BMP-10 was examined in a cohort of human breast cancer specimen (normal, n=23; cancer, n=97), using both quantitative real time PCR and immunohistochemical staining. Levels of BMP-10 transcripts were correlated with clinical and pathological, together with clinical outcome information of the patients. A human BMP-10 expression construct was used to transfect breast cancer cells (MDA-MB-231, negative in BMP-10 expression). The expression of BMP-10 in the transfected cells was verified using RT-PCR and western blot. The effect of BMP-10 expression on growth of MDA-MB-231 cells was investigated using an in vitro growth assay.
 Results: Immunohistochemical staining revealed a decreased protein expression of BMP-10 in breast cancer cells, compared with normal mammary epithelial cells. The quantitative real time PCR further demonstrated that low levels of the BMP-10 transcripts correlated to poor prognosis. Tumours form patients with good prognostic index (NPI<3.4) had significantly higher levels of BMP-10 transcripts, compared with those from poor prognostic index (NPI>5.4) (p=0.045). In addition, patients who died of breast cancer showed a significantly lower levels of the transcript compared with those who remained disease free (p=0.027). Mean disease free survival of the patients with higher level of BMP-10 was 132.8 (122.0-143.5, 95% CI) months, which was significantly longer compared to 93.7 (60.3-127.2) months of patients with lower level of BMP-10 expression, p=0.043 using Kaplan-Meirer survival analysis. An inhibitory effect on cell growth by over-expression of BMP-10 was seen in the breast cancer cells. The absorbance of MDA-MB-231 BMP-10 over-expressing (MDA-MB-231BMP-10exp) cells of Day 5 is 1.40±0.19, p<0.01 vs both MDA-MB-231 wild type (MDA-MB-231WT, 2.17±0.11) and empty vector control (MDA-MB-231pEF/His, 1.83±0.17).
 Conclusions: Taken together, BMP-10 can inhibit the cell growth of breast cancer cells. A decrease in BMP-10 expression correlates with poor prognosis of patients with breast cancer. BMP-10 may function as tumor suppressor in breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4068.