UNIGE document Scientific Article
previous document  unige:19476  next document
add to browser collection
Title

miR-200 enhances mouse breast cancer cell colonization to form distant metastases

Authors
Dykxhoorn, Derek M.
Wu, Yichao
Xie, Huangming
Yu, Fengyan
Lal, Ashish
Petrocca, Fabio
Song, Erwei
show hidden authors show all authors [1 - 10]
Published in PLOS ONE. 2009, vol. 4, no. 9, p. e7181
Abstract BACKGROUND: The development of metastases involves the dissociation of cells from the primary tumor to penetrate the basement membrane, invade and then exit the vasculature to seed, and colonize distant tissues. The last step, establishment of macroscopic tumors at distant sites, is the least well understood. Four isogenic mouse breast cancer cell lines (67NR, 168FARN, 4TO7, and 4T1) that differ in their ability to metastasize when implanted into the mammary fat pad are used to model the steps of metastasis. Only 4T1 forms macroscopic lung and liver metastases. Because some miRNAs are dysregulated in cancer and affect cellular transformation, tumor formation, and metastasis, we examined whether changes in miRNA expression might explain the differences in metastasis of these cells. METHODOLOGY/PRINCIPAL FINDINGS: miRNA expression was analyzed by miRNA microarray and quantitative RT-PCR in isogenic mouse breast cancer cells with distinct metastatic capabilities. 4T1 cells that form macroscopic metastases had elevated expression of miR-200 family miRNAs compared to related cells that invade distant tissues, but are unable to colonize. Moreover, over-expressing miR-200 in 4TO7 cells enabled them to metastasize to lung and liver. These findings are surprising since the miR-200 family was previously shown to promote epithelial characteristics by inhibiting the transcriptional repressor Zeb2 and thereby enhancing E-cadherin expression. We confirmed these findings in these cells. The most metastatic 4T1 cells acquired epithelial properties (high expression of E-cadherin and cytokeratin-18) compared to the less metastatic cells. CONCLUSIONS/SIGNIFICANCE: Expression of miR-200, which promotes a mesenchymal to epithelial cell transition (MET) by inhibiting Zeb2 expression, unexpectedly enhances macroscopic metastases in mouse breast cancer cell lines. These results suggest that for some tumors, tumor colonization at metastatic sites might be enhanced by MET. Therefore the epithelial nature of a tumor does not predict metastatic outcome.
Keywords 3' Untranslated RegionsAnimalsCadherins/biosynthesisCell Line, TumorCell Transformation, NeoplasticCloning, MolecularEpithelium/metabolismFemaleHomeodomain Proteins/metabolismKruppel-Like Transcription Factors/metabolismMammary Neoplasms, Animal/*genetics/*metabolismMiceMicroRNAs/*metabolismMicroscopy, Fluorescence/methodsNeoplasm MetastasisTreatment Outcome
Identifiers
PMID: 19787069
Full text
Article - public document Free access
Structures
Research group ROS in CTL mediated cell death : from mechanism to applications (898)
Citation
(ISO format)
DYKXHOORN, Derek M. et al. miR-200 enhances mouse breast cancer cell colonization to form distant metastases. In: PLOS ONE, 2009, vol. 4, n° 9, p. e7181. https://archive-ouverte.unige.ch/unige:19476

307 hits

124 downloads

Update

Deposited on : 2012-04-23

Export document
Format :
Citation style :