Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	BRAF(V600E) Efficient Transformation and Induction of Microsatellite Instability Versus KRAS(G12V) Induction of Senescence Markers in Human Colon Cancer Cells
Δημιουργός/Συγγραφέας:	Oikonomou, Eftychia Makrodouli, Eleni Evagelidou, Maria Joyce, Tobias Probert, Lesley [EL] Πίντζας, Αλέξανδρος[EN] Pintzas, Alexander
Εκδότης:	Neoplasia Press
Τόπος έκδοσης:	Ann Arbor
Ημερομηνία:	2009-11
Γλώσσα:	Αγγλικά
ISSN:	1522-8002
DOI:	10.1593/neo.09514
Περίληψη:	In colorectal cancer, BRAF and KRAS oncogenes are mutated in about 15% and 35% respectively at approximately the same stage of the adenoma-carcinoma sequence. Since these two mutations rarely coexist, further analysis to dissect their function of transformation in colon cancer is required. Caco-2 human colon adenocarcinoma cells were stably transfected with BRAF(V600E) (Caco-BR cells) or KRAS(G12V) (Caco-K cells) oncogenes. BRAF(V600E) is more efficient in transforming Caco-2 cells and altering their morphology. The dominant nature of BRAF(V600E) is evident by its ability to render Caco-2 cells tumorigenic in vivo all be it through selective extracellular signal-related kinase (ERK) 2 phosphorylation and high levels of cyclin D1. As a consequence, the cell cycle distribution of parental cells is altered and microsatellite instability is introduced. Attenuated ERK activation observed correlated with KSR downregulation by BRAF(V600E) without further implications to signaling. Highly activated ERK in case of KRAS(G12V) (Caco-K cells) leads to mild transformation causing Caco-K cells to express premature senescence-related markers and acquire growth factor-dependent viability. Interestingly, BRAF(WT) gets equally activated by upstream KRAS mutations present in colon adenocarcinoma cells such as DLD-1 and SW620. Taken together, these results suggest that the two oncogenes have different transforming capability in colon cancer, although they both use the mitogen-activated protein (MAP) kinase pathway to carry out their effect. In general, BRAF(V600E) presents greater potential in mediating tumorigenic effect as compared to KRAS(G12)V both in vivo and in vitro. These findings may have implications in personalised diagnosis and targeted therapeutics.
Τίτλος πηγής δημοσίευσης:	Neoplasia
Τόμος/Κεφάλαιο:	11
Τεύχος:	11
Σελίδες:	1116-1131
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens)
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Όροι και προϋποθέσεις δικαιωμάτων:	This article appears in: Neoplasia, v11, issue11, p.1116-1131 and can be found at the following URL on the Neoplasia Press website: http://dx.doi.org/10.1593/neo.09514
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Βιολογικών Ερευνών και Βιοτεχνολογίας (ΙΒΕΒ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο