Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Elucidating the identity of resistance mechanisms to prednisolone exposure in acute lymphoblastic leukemia cells through transcriptomic analysis:A computational approach
Δημιουργός/Συγγραφέας:	Sifakis, Emmanouil G. Lambrou, George I. Prentza, Andriana Vlahopoulos, Spiros Koutsouris, Dimitris Tzortzatou-Stathopoulou, Fotini [EL] Χατζηιωάννου, Αριστοτέλης[EN] Chatziioannou, Aristotelis
Εκδότης:	Biomed Central
Ημερομηνία:	2011-12-20
Γλώσσα:	Αγγλικά
Περίληψη:	Background It has been shown previously that glucocorticoids exert a dual mechanism of action, entailing cytotoxic, mitogenic as well as cell proliferative and anti-apoptotic responses, in a dose-dependent manner on CCRF-CEM cells at 72 h. Early gene expression response implies a dose-dependent dual mechanism of action of prednisolone too, something reflected on cell state upon 72 h of treatment. Methods In this work, a generic, computational microarray data analysis framework is proposed, in order to examine the hypothesis, whether CCRF-CEM cells exhibit an intrinsic or acquired mechanism of resistance and investigate the molecular imprint of this, upon prednisolone treatment. The experimental design enables the examination of both the dose (0 nM, 10 nM, 22 uM, 700 uM) effect of glucocorticoid exposure and the dynamics (early and late, namely 4 h, 72 h) of the molecular response of the cells at the transcriptomic layer. Results In this work, we demonstrated that CCRF-CEM cells may attain a mixed mechanism of response to glucocorticoids, however, with a clear preference towards an intrinsic mechanism of resistance. Specifically, at 4 h, prednisolone appeared to down-regulate apoptotic genes. Also, low and high prednisolone concentrations up-regulates genes related to metabolism and signal-transduction in both time points, thus favoring cell proliferative actions. In addition, regulation of NF-κB-related genes implies an inherent mechanism of resistance through the established link of NF-κB inflammatory role and GC-induced resistance. The analysis framework applied here highlights prednisolone-activated regulatory mechanisms through identification of early responding sets of genes. On the other hand, study of the prolonged exposure to glucocorticoids (72 h exposure) highlights the effect of homeostatic feedback mechanisms of the treated cells. Conclusions Overall, it appears that CCRF-CEM cells in this study exhibit a diversified, combined pattern of intrinsic and acquired resistance to prednisolone, with a tendency towards inherent resistant characteristics, through activation of different molecular courses of action.
Τίτλος πηγής δημοσίευσης:	Journal of Clinical Bioinformatics
Τόμος/Κεφάλαιο:	1
Τεύχος:	36
Σελίδες:	21
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens)
Λέξεις-Κλειδιά:	Acute lymphoblastic leukemia DNA microarray analysis Gene ontology Glucocorticoid resistance Intrinsic vs. acquired
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
EU Grant identifier:	info:eu-repo/grantAgreement/EC/FP7/231519
Κάτοχος πνευματικών δικαιωμάτων:	© 2011 Sifakis et al; licensee BioMed Central Ltd.
Όροι και προϋποθέσεις δικαιωμάτων:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	http://www.jclinbioinformatics.com/content/1/1/36
Ηλεκτρονική διεύθυνση περιοδικού (link) :	http://www.jclinbioinformatics.com
Σημειώσεις:	Ερευνητικη ομάδα ΕΙΕ: bioinformatics Published in the frame of project: e-LICO-FP7-231519
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Βιολογικών Ερευνών και Βιοτεχνολογίας (ΙΒΕΒ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο