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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The majority of breast cancer related deaths occur as a result of metastasis. The failure of effective treatments for metastasis is the underlying cause for this. Much remains unknown about the process of metastasis and how best to prevent or treat metastatic breast cancer. Therefore, a better understanding of the metastatic process is needed in order to determine effective therapeutic interventions to either eradicate, or slow down metastatic outgrowth of breast cancer. Metastasis is an inefficient process, however the ability of only a small number of cells to complete this process may have serious, life-threatening consequences. Little is known about whether expression of the metastasis suppressor breast cancer metastasis suppressor 1 (BRMS1) can suppress metastatic outgrowth in different organs in multiple experimental models of metastasis, or what effect BRMS1 expression has on the various steps in metastatic cascade. In this study we investigated the effect of BRMS1 expression on organ-specific metastasis. In addition, the steps in metastasis that are inhibited by BRMS1-expression were determined. In vivo, BRMS1 expression reduced metastatic burden to liver, bone, brain, and lung in mice by at least 75% (P<0.05). Detailed quantitative analysis of the metastatic process in lung showed that BRMS1 expression significantly reduced the numbers of solitary single cells that survive after initial arrest within the lung microvasculature, and also inhibited the initiation of growth subsequent to arrest. In vitro, BRMS1 expression decreased cancer cell survival under stress conditions (hypoxia), increased anoikis, and decreased the ability of cancer cells to adhere. These novel findings demonstrate that BRMS1 is a potent suppressor of metastasis in multiple organs, and identify two steps in the metastatic process that are sensitive to inhibition by BRMS1.
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PMID:BRMS1 suppresses breast cancer metastasis in multiple experimental models of metastasis by reducing solitary cell survival and inhibiting growth initiation. 1854 67

Human growth hormone (hGH) plays critical roles in pubertal mammary gland growth, development, and sexual maturation. Accumulated studies have reported that autocrine/paracrine hGH is an orthotopically expressed oncoprotein that promotes normal mammary epithelial cell oncogenic transformation. Autocrine/paracrine hGH has also been reported to promote mammary epithelial cell epithelial-mesenchymal transition (EMT) and invasion. However, the underlying mechanism remains largely obscure. MicroRNAs (miRNAs) are reported to be involved in regulation of multiple cellular functions of cancer. To determine whether autocrine/paracrine hGH promotes EMT and invasion through modulation of miRNA expression, we performed microarray profiling using MCF-7 cells stably expressing wild type or a translation-deficient hGH gene and identified miR-96-182-183 as an autocrine/paracrine hGH-regulated miRNA cluster. Forced expression of miR-96-182-183 conferred on epithelioid MCF-7 cells a mesenchymal phenotype and promoted invasive behavior in vitro and dissemination in vivo. Moreover, we observed that miR-96-182-183 promoted EMT and invasion by directly and simultaneously suppressing BRMS1L (breast cancer metastasis suppressor 1-like) gene expression. miR-96 and miR-182 also targeted GHR, providing a potential negative feedback loop in the hGH-GHR signaling pathway. We further demonstrated that autocrine/paracrine hGH stimulated miR-96-182-183 expression and facilitated EMT and invasion via STAT3 and STAT5 signaling. Consistent with elevated expression of autocrine/paracrine hGH in metastatic breast cancer tissue, miR-96-182-183 expression was also remarkably enhanced. Hence, we delineate the roles of the miRNA-96-182-183 cluster and elucidate a novel hGH-GHR-STAT3/STAT5-miR-96-182-183-BRMS1L-ZEB1/E47-EMT/invasion axis, which provides further understanding of the mechanism of autocrine/paracrine hGH-stimulated EMT and invasion in breast cancer.
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PMID:Autocrine/Paracrine Human Growth Hormone-stimulated MicroRNA 96-182-183 Cluster Promotes Epithelial-Mesenchymal Transition and Invasion in Breast Cancer. 2587 90

Our aim is to investigate whether or not the breast cancer metastasis suppressor 1 (BRMS1) gene expression is directly linked to clinico-pathological features of breast cancer. Following a stringent inclusion and exclusion criteria, case-control studies with associations between BRMS1 and breast cancer were selected from articles obtained by way of searches conducted through an electronic database. All statistical analyses were performed with Stata 12.0 (Stata Corp, College Station, TX, U.S.A.). Ultimately, 1,263 patients with breast cancer were found in a meta-analysis retrieved from a total that included 12 studies. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was significantly lower in comparison with normal breast tissues (odds ratio, OR = 0.08, 95% confidence interval (CI) = 0.04-0.15). The BRMS1 protein in metastatic breast cancer tissue was decreased than from that was found in non-metastatic breast cancer tissue (OR = 0.20, 95%CI = 0.13-0.29), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1 and 2 was found to be higher than TNM stages 3 and 4 (OR = 4.62, 95%CI = 2.77-7.70). BRMS1 protein in all three major types of breast cancer was lower than that of control tissues respectively. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. The results our meta-analysis showed that reduction in BRMS1 expression level was linked directly to clinico-pathological features of breast cancer significantly; therefore, suggesting the loss of expression or reduced levels of BRMS1 is potentially a strong indicator of the metastatic capacity of breast cancer with poor prognosis.
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PMID:BRMS1 gene expression may be associated with clinico-pathological features of breast cancer. 2853 25