Purpose: Keratin19 (KRT19) is the smallest known type I intermediate filament and is used as a marker for RT-PCR-mediated detection of disseminated tumors. In this study, we investigated the functional analysis of KRT19 in human breast cancer. Experimental Design: Using a shRNA 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 up-regulation of Akt signaling as a result of reduced PTEN mRNA expression. Silencing of KRT19 decreased nuclear import of early growth response-1 (Egr1), a transcriptional factor for PTEN transcription, through reduced association between Egr1 and importin-7 (Imp7). 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.
- Received October 21, 2012.
- Revision received May 31, 2013.
- Accepted June 5, 2013.
- Copyright © 2013, American Association for Cancer Research.