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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

Authors 

J H JuW YangK M LeeS OhK NamS ShimS Y ShinM C GyeIn-Sun ChuI Shin

Publisher 

American Association for Cancer Research

Issue Date 

2013

Citation 

Clinical Cancer Research, vol. 19, no. 16, pp. 4335-4346

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

Link 

http://dx.doi.org/10.1158/1078-0432.CCR-12-3295

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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