Bone morphogenetic protein-10 (BMP-10) inhibits aggressiveness of breast cancer cells and correlates with poor prognosis in breast cancer.
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.
Ye
Lin
L
Department of Surgery, Cardiff University School of Medicine, Cardiff, UK. yel@cf.ac.uk
Bokobza
Sivan
S
Li
Jin
J
Moazzam
Muhammad
M
Chen
Jinfeng
J
Mansel
Robert E
RE
Jiang
Wen G
WG
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis
C541386:BMP10 protein, human; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen