Bone morphogenetic protein 7 is widely overexpressed in primary breast cancer
ABSTRACT Bone morphogenetic proteins (BMP) make up a family of extracellular signaling molecules that play a critical role in vertebrate development and both inhibit and stimulate growth in cancer cells. BMP7 was recently identified in our genomewide copy number and expression survey as being activated through amplification in breast cancer cell lines. In the present study, we further explored BMP7 gene copy number and expression changes in 22 breast cancer cell lines and 146 primary breast tumors. FISH analysis revealed that BMP7 copy number varied greatly from one cell line to another, with three cell lines showing extremely high-level amplification. Among primary tumors, BMP7 copy number was increased in 16% of the cases. BMP7 mRNA expression was determined in the cell lines and in a subset of 44 tumor samples by RT-PCR or quantitative real-time RT-PCR, respectively. Despite elevated mRNA levels in cancer cells, there was no significant association between copy number increase and mRNA expression, even though the highest expression was seen in cell lines and tumors with increased BMP7 copy number. Most interestingly, immunohistochemical analysis revealed BMP7 protein staining in all 11 breast cancer cell lines examined and strongly elevated BMP7 protein expression in 71.4% of the tumor samples as compared to normal mammary epithelium. Our results illustrate the frequent involvement of BMP7 alterations in breast cancer and especially highlight overexpression of the BMP7 protein in a very large fraction of primary breast tumors, thus suggesting a possible functional role for BMP7 in breast cancer development.
SourceAvailable from: Lin Ye
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ABSTRACT: BACKGROUND: Our previous study showed that BMP7 revealed significantly higher levels in esophageal squamous cell carcinoma (ESCC) tissues with lymph node metastasis compared with non-lymph node metastasis, using gene expression profiling assays. The roles of BMP7 in ESCC is not fully understood. AIM: The aim of this study was to investigate the effect of BMP7 on lymph node metastasis of ESCC and to explore its potential mechanism. METHODS: Expression of BMP7 in ESCC tissues was evaluated by immunohistochemistry. BMP7 were down-regulated by RNA interference. The protein and mRNA levels of BMP7 were detected by western blot and RT-PCR, respectively. High content screening and transwell assay were used to identify the metastatic ability of tumor cells. RESULTS: Positivity of BMP7 staining was 57.5 % in the tissues of primary carcinoma with lymph node metastasis compared to tissues without lymph node metastasis, and expression of BMP7 was significantly higher in the cell lines with highly metastatic capacity than that in the cell lines without metastatic ability. Suppression of endogenous BMP7 expression by siRNA in the highly metastatic cell lines resulted in significant reduction in ability of cell migration and invasion in both in vitro and in vivo studies. In addition, inhibition of BMP7 by siRNA also leads to up-regulation of E-cadherin and down-regulation of MMP-9 in the highly metastatic cell lines. CONCLUSIONS: These findings indicate that BMP7 modulates the expression of E-cadherin and MMP-9, and by which mechanism it may regulate cell migration and metastasis of ESCCs.Digestive Diseases and Sciences 03/2013; 58(7). DOI:10.1007/s10620-013-2611-3 · 2.55 Impact Factor