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Supplementary Figure 4 - PDF file 1098K, KRT19 inhibition does not down-regulate PTEN protein level through modulation of PTEN stability

Supplementary Figure 6 - PDF file 1339K, Statistical analyses of western blots and RT-PCR data

Supplementary Information - PDF file 163K, Legends to Supplementary data and Materials and Methods

Supplementary Fig. 7A - PDF file 188K, Correlation between KRT19 and HER2 expression in breast cancer patient samples

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. Clin Cancer Res; 19(16); 4335–46. ©2013 AACR.

Supplementary Figure 5 - PDF file 2097K, KRT19 regulated nuclear localization of Egr1 transcriptional factor

Supplementary Fig. 3 - PDF file 2033K, KRT19 inhibition induces Akt activity through down-regulation of PTEN expression.

Supplementary Fig. 2 - PDF file 2822K, KRT19 inhibition up-regulates colony formation, cell migration and invasion