Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	A Tumor-Protective Role for Human Kallikrein-Related Peptidase 6 in Breast Cancer Mediated by Inhibition of Epithelial-to-Mesenchymal Transition
Δημιουργός/Συγγραφέας:	Pampalakis, Georgios Prosnikli, Evangelia Agalioti, Theodora Vlahou, Antonia [EL] Ζουμπουρλής, Βασίλης[EN] Zoumpourlis, Vassilis Sotiropoulou, Georgia
Εκδότης:	American Association for Cancer Research (A A C R)
Τόπος έκδοσης:	PHILADELPHIA
Ημερομηνία:	2009-05-01
Γλώσσα:	Αγγλικά
ISSN:	0008-5472
DOI:	10.1158/0008-5472.CAN-08-1976
Περίληψη:	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 KLK6 gene in metastatic breast cancer and its putative implications for tumor progression. We present evidence that tumor-specific loss of KLK6 expression is due to hypermethylation of specific CpGs located in the KLK6 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 KLK6 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 calreticutin 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.
Τίτλος πηγής δημοσίευσης:	Cancer Research
Τόμος/Κεφάλαιο:	69
Τεύχος:	9
Σελίδες:	3779-3787
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens)
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© AMER ASSOC CANCER RESEARCH
Ηλεκτρονική διεύθυνση περιοδικού (link) :	http://cancerres.aacrjournals.org/
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Βιολογικών Ερευνών και Βιοτεχνολογίας (ΙΒΕΒ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο