Deregulation of MicroRNA Expression in Metastatic Breast Cancer of Mice and Women
M Lacroix-Triki, G Maillot, S Beck, L Roger, P Zindy, T Filleron, H Roche, S Vagner. Institute Claudius Regaud, Toulouse, France
Background: miRNAs are short noncoding RNAs which trigger translational down-regulation or increased degradation of the target mRNA. If recent studies have shown altered miRNA expression in cancer, few ones explore the role of miRNAs in the metastatic process. Using high-throughput technologies, we have studied miRNAs expression in a mouse model of metastatic mammary cancer, and in a series of breast cancers.
Design: The mouse model consisted of orthotopic injection of 4 mammary cancer cell lines, giving rise to tumors with different metastatic potential. 67NR tumors showed no metastasis, 168FARN and 4T0 tumors had intermediate invasive potential, whereas 4T1 tumors led to lung metastasis. Thirty mice were injected, tumors were harvested and total RNA extracted. High-throughput miRNAs profiling was performed using microarray in collaboration with the EMBL facility (V. Benes). Expression of selected miRNAs was validated by northern blot and quantitative RT-PCR. In addition to miR-10b, we focused on 3 miRNAs highly expressed in the metastatic tumors 4T1, and studied their expression in 34 metastatic and non-metastatic breast cancers, using RT-qPCR. miRNAs expression was correlated to clinico-pathological data, with special regards to the distant metastatic outcome.
Results: Microarray analysis of the 30 mouse tumors allowed identification of a set of 47 miRNAs that could accurately classify each tumor.
Each tumor type was characterized by a specific cluster of over-expressed miRNAs, which was cross-validated by northern blot and RT-qPCR analysis. Among the 4 selected miRNAs that were highly expressed in the metastatic tumor 4T1, one showed a significant association to metastatic outcome in our series of 34 invasive breast cancers.
Conclusions: In a translational study from a metastatic mouse model to human tumors, we could identify miRNAs with altered expression in metastatic breast cancer, thus providing new insights in the complex deregulation of gene expression leading to metastatic progression.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 219, Tuesday Morning