Regulation of cell proliferation and migration by keratin19-induced nuclear import of early growth response-1 in breast cancer cells

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Title
Regulation of cell proliferation and migration by keratin19-induced nuclear import of early growth response-1 in breast cancer cells
Author(s)
J H Ju; W Yang; K M Lee; S Oh; K Nam; S Shim; S Y Shin; M C Gye; In-Sun Chu; I Shin
Bibliographic Citation
Clinical Cancer Research, vol. 19, no. 16, pp. 4335-4346
Publication Year
2013
Abstract
Purpose: Keratin19 (KRT19) is the smallest known type I intermediate filament and is used as a marker for reverse transcriptase PCR-mediated detection of disseminated tumors. In this study, we investigated the functional analysis of KRT19 in human breast cancer. Experimental Design: Using a short hairpin RNA system, we silenced KRT19 in breast cancer cells. KRT19 silencing was verified by Western blot analysis and immunocytochemistry. We further examined the effect of KRT19 silencing on breast cancer cells by cell proliferation, migration, invasion, colony formation assay, cell-cycle analysis, immunocytochemistry, immunohistochemistry, and mouse xenograft assay. Results: Silencing of KRT19 resulted in increased cell proliferation, migration, invasion, and survival. These effects were mediated by upregulation of Akt signaling as a result of reduced PTEN mRNA expression. Silencing of KRT19 decreased the nuclear import of early growth response-1 (Egr1), a transcriptional factor for PTEN transcription, through reduced association between Egr1 and importin-7. We also confirmed that silencing of KRT19 increased tumor formation in a xenograft model. Conclusions: KRT19 is a potential tumor suppressor that negatively regulates Akt signaling through modulation of Egr1 nuclear localization.
ISSN
1078-0432
Publisher
Amer Assoc Cancer Research
DOI
http://dx.doi.org/10.1158/1078-0432.CCR-12-3295
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
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