miR-200 Enhances Mouse Breast Cancer Cell Colonization to Form Distant Metastases

• DOI: 10.1371/journal.pone.0007181
• Publication Date: 2009-09-28T22:38:19Z
• Authors: Derek M. Dykxhoorn; Yichao Wu; Huangming Xie; Fengyan Yu; Ashish Lal; Fabio Petrocca; Denis Martinvalet; Erwei Song; Bing Lim; Judy Lieberman
• Keywords: 0301 basic medicine; Science; Kruppel-Like Transcription Factors; 610; Mammary Neoplasms, Animal; MicroRNAs/*metabolism; Epithelium; Cadherins/biosynthesis; Mice; 03 medical and health sciences; Cell Line, Tumor; Homeodomain Proteins/metabolism; Animals; info:eu-repo/classification/ddc/612; Cloning, Molecular; Neoplasm Metastasis; ddc:612; 3' Untranslated Regions; Microscopy, Fluorescence/methods; Homeodomain Proteins; Q; R; Zinc Finger E-box-Binding Homeobox 1; Cadherins; 3. Good health; Epithelium/metabolism; 3' Untranslated Regions; Animals; Cadherins; Cell Line, Tumor; Cell Transformation, Neoplastic; Cloning, Molecular; Epithelium; Female; Homeodomain Proteins; Kruppel-Like Transcription Factors; Mammary Neoplasms, Animal; Mice; MicroRNAs; Microscopy, Fluorescence; Neoplasm Metastasis; Treatment Outcome; Zinc Finger E-box-Binding Homeobox 1; Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all); MicroRNAs; Cell Transformation, Neoplastic; Treatment Outcome; Microscopy, Fluorescence; Medicine; Female; Mammary Neoplasms, Animal/*genetics/*metabolism; Kruppel-Like Transcription Factors/metabolism; Research Article

Background The development of metastases involves the dissociation cells from primary tumor to penetrate basement membrane, invade and then exit vasculature seed, colonize distant tissues. last step, establishment macroscopic tumors at sites, is least well understood. Four isogenic mouse breast cancer cell lines (67NR, 168FARN, 4TO7, 4T1) that differ in their ability metastasize when implanted into mammary fat pad are used model steps metastasis. Only 4T1 forms lung liver metastases. Because some miRNAs dysregulated affect cellular transformation, formation, metastasis, we examined whether changes miRNA expression might explain differences metastasis these cells. Methodology/Principal Findings was analyzed by microarray quantitative RT–PCR with distinct metastatic capabilities. form had elevated miR-200 family compared related tissues, but unable colonize. Moreover, over-expressing 4TO7 enabled them liver. These findings surprising since previously shown promote epithelial characteristics inhibiting transcriptional repressor Zeb2 thereby enhancing E-cadherin expression. We confirmed most acquired properties (high cytokeratin-18) less Conclusions/Significance Expression miR-200, which promotes a mesenchymal transition (MET) expression, unexpectedly enhances lines. results suggest for tumors, colonization sites be enhanced MET. Therefore nature does not predict outcome.