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- W4361243885 abstract "<div>Abstract<p>Human kallikrein-related peptidase 6 (KLK6) was cloned as a putative class II tumor suppressor based on its inactivated expression in metastatic breast cancer. Here, we investigated the mechanism(s) underlying the silencing of <i>KLK6</i> gene in metastatic breast cancer and its putative implications for tumor progression. We present evidence that tumor-specific loss of <i>KLK6</i> expression is due to hypermethylation of specific CpGs located in the <i>KLK6</i> proximal promoter. Methylation-dependent binding of methyl CpG-binding protein 2 and the formation of repressive chromatin mediated by localized histone deacetylation are critical components of <i>KLK6</i> silencing in breast tumors. Re-expression of KLK6 in nonexpressing MDA-MB-231 breast tumor cells by stable cDNA transfection resulted in marked reversal of their malignant phenotype, manifested by lower proliferation rates and saturation density, marked inhibition of anchorage-independent growth, reduced cell motility, and their dramatically reduced ability to form tumors when implanted in severe combined immunodeficiency mice. Interestingly, inhibition of tumor growth was observed at physiologic concentrations of KLK6, but not when KLK6 was highly overexpressed, as observed in a subset of breast tumors. Differential proteomic profiling revealed that KLK6 re-expression results in significant down-regulation of vimentin which represents an established marker of epithelial-to-mesenchymal transition of tumor cells and in concomitant up-regulation of calreticulin and epithelial markers cytokeratin 8 and 19, indicating that KLK6 may play a protective role against tumor progression that is likely mediated by inhibition of epithelial-to-mesenchymal transition. We suggest that KLK6 is an epigenetically regulated tumor suppressor in human breast cancer and provide ways of pharmacologic modulation. [Cancer Res 2009;69(9):3779–87]</p></div>" @default.
- W4361243885 created "2023-03-31" @default.
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- W4361243885 date "2023-03-30" @default.
- W4361243885 modified "2023-10-14" @default.
- W4361243885 title "Data from A Tumor-Protective Role for Human Kallikrein-Related Peptidase 6 in Breast Cancer Mediated by Inhibition of Epithelial-to-Mesenchymal Transition" @default.
- W4361243885 doi "https://doi.org/10.1158/0008-5472.c.6499413.v1" @default.
- W4361243885 hasPublicationYear "2023" @default.
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