Department of Surgery, Cardiff University School of Medicine, Cardiff, UK.
Cancer Sci. 2010 Oct;101(10):2137-44. doi: 10.1111/j.1349-7006.2010.01648.x. Epub 2010 Jul 1.
Our recent study showed that a novel member of bone morphogenetic protein (BMP) family, BMP-10, was decreased in prostate cancer. In the present study, we investigated the implication of BMP-10 in breast cancer, particularly the relation of its expression with clinical aspects. The expression of BMP-10 was examined in a cohort of human breast cancer specimens (normal, n = 23; cancer, n = 97), using both quantitative real-time PCR and immunohistochemical staining. The full-length human BMP-10 was cloned into a mammalian expression plasmid vector and then transfected into breast cancer cells. The effect on growth, cell matrix adhesion, motility, and invasion of MDA-MB-231 cells by BMP-10 was then investigated using in vitro growth assays. Immunohistochemical staining and quantitative real-time PCR revealed a decreased expression of BMP-10 in breast cancer. Further analysis of BMP-10 transcript level against the clinical aspect demonstrated that the decreased BMP-10 expression correlated with disease progression, bone metastasis, and poor prognosis. The disease-free survival of the patients with a higher level of BMP-10 was 132.8 (95% CI, 122.0-143.5) months, significantly longer compared to 93.7 (95% CI, 60.3-127.2) months for patients with a lower level of BMP-10 expression (P = 0.043). The overexpression of BMP-10 has broad inhibitory effects on the in vitro growth, invasion, and motility of breast cancer cells. Taken together, BMP-10 can inhibit the cell growth of breast cancer cells, and decreased BMP-10 expression correlates to poor prognosis and disease progression, particularly the lymphatic and bone metastasis. Bone morphogenetic protein-10 (BMP-10) may function as a tumor suppressor in breast cancer.
我们最近的研究表明,骨形态发生蛋白(BMP)家族的一个新成员 BMP-10 在前列腺癌中减少。在本研究中,我们研究了 BMP-10 在乳腺癌中的意义,特别是其表达与临床方面的关系。使用定量实时 PCR 和免疫组织化学染色检测了人类乳腺癌标本(正常,n=23;癌症,n=97)中 BMP-10 的表达。将全长人 BMP-10 克隆到哺乳动物表达质粒载体中,然后转染到乳腺癌细胞中。然后使用体外生长测定研究 BMP-10 对 MDA-MB-231 细胞生长、细胞基质粘附、运动和侵袭的影响。免疫组织化学染色和定量实时 PCR 显示乳腺癌中 BMP-10 的表达降低。进一步分析 BMP-10 转录水平与临床方面的关系表明,BMP-10 表达的降低与疾病进展、骨转移和预后不良相关。BMP-10 水平较高的患者的无病生存率为 132.8(95%CI,122.0-143.5)个月,明显长于 BMP-10 水平较低的患者的 93.7(95%CI,60.3-127.2)个月(P=0.043)。BMP-10 的过表达对乳腺癌细胞的体外生长、侵袭和运动具有广泛的抑制作用。总之,BMP-10 可抑制乳腺癌细胞的生长,BMP-10 表达降低与预后不良和疾病进展相关,特别是淋巴和骨转移。骨形态发生蛋白-10(BMP-10)可能在乳腺癌中作为肿瘤抑制因子发挥作用。