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Krell J.,MRC Cyclotron Building | Frampton A.E.,Imperial College London | Jacob J.,MRC Cyclotron Building | Pellegrino L.,MRC Cyclotron Building | And 7 more authors.
Molecular Diagnosis and Therapy | Year: 2012

Background: MicroRNAs (miRNAs) may function as suppressors or promoters of tumor metastasis according to their messenger RNA targets. Previous studies have suggested that miR-9 and miR-151-5p are associated with metastasis in breast cancer and hepatocellular carcinoma, respectively. We aimed to further establish the potential roles of miR-9 and miR-151-5p in tumor invasion and metastasis and investigate their use as biomarkers. Methods: We used quantitative real-time PCR (qRT-PCR) to measure differences in miR-9 and miR-151-5p expression between primary breast tumors and their lymph-node metastases in 194 paired tumor samples from 97 patients. We also correlated expression levels with histologic data to investigate their utility as biomarkers. Results: There were no significant differences in miR-9 expression between the primary tumors and lymph nodes; however, miR-151-5p expression was significantly lower in the lymph-node metastases than in their corresponding tumors (p < 0.05). miR-9 levels were elevated in primary breast tumors from patients diagnosed with higher-grade tumors (p < 0.05); however, no differences were observed in miR-151-5p levels between different grades of tumor. Interestingly, miR-9 levels were elevated in invasive lobular carcinomas (ILC) compared with invasive ductal carcinomas (IDC; p < 0.01). Conclusions: In aggregate, these data suggest that miR-151-5p upregulation may suppress metastasis in primary breast tumors. Both miRNAs may serve as useful biomarkers in future clinical trials in breast cancer. © 2012 Springer International Publishing AG. All rights reserved. Source

Jacob J.,MRC Cyclotron Building | Frampton A.E.,Imperial College London | Castellano L.,MRC Cyclotron Building | Stebbing J.,Imperial College London | Krell J.,MRC Cyclotron Building
Expert Review of Anticancer Therapy | Year: 2012

Evaluation of: Arima Y, Hayashi H, Sasaki M et al. Induction of ZEB by inactivation of RB is a key determinant of the mesenchymal phenotype of breast cancer. J. Biol. Chem. 287(11), 7896-7906 (2012). Retinoblastoma protein (RB) is one of the most important tumor suppressors and functions in multiple biological pathways that are deregulated during tumor initiation and progression. Epithelial-to-mesenchymal transition (EMT) is a reversible embryonic process by which epithelial cells lose cell-cell contact and polarity, and its aberrant activation can trigger tumor progression and metastasis. Previously, it has been shown that depletion of RB initiates EMT by downregulating the adhesion molecule E-cadherin. The evaluated article suggests that RB inactivation contributes to loss of cell cycle control and also leads to downregulation of the miR-200 family, thereby causing upregulation of ZEB expression and consequently EMT by downregulation of E-cadherin. RB inactivation could be a key event underlying the mesenchymal and aggressive phenotype of triple-negative breast cancer. Furthermore, exploring links between RB inactivation and EMT might reveal new therapeutic targets for triple-negative breast cancer. © 2012 Expert Reviews Ltd. Source

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