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Glucocorticoids (GCs) induce cell cycle arrest and apoptosis in lymphoid cells and constitute a central component in the treatment of lymphoid malignancies. The molecular basis of this clinically important phenomenon remains. | Turkish Journal of Biology Turk J Biol (2014) 38: 956-959 © TÜBİTAK doi:10.3906/biy-1404-34 http://journals.tubitak.gov.tr/biology/ Short Communication PLZF overexpression in T-ALL cell line CEM-C7H2-2C8 downregulates glucocorticoid receptor (GR) and its target genes 1, 2 1 Muhammad WASIM *, Muhammad MANSHA , Muhammad TAYYAB , 1 1 3 1 Ali Raza AWAN , Sehrish FIRYAL , Christine MANTINGER , Tahir YAQUB 1 Institute of Biochemistry and Biotechnology, University of Veterinary and Animal Sciences, Lahore, Pakistan 2 Department of Zoology, Division of Science and Technology, University of Education, Lahore, Pakistan 3 Tyrolean Cancer Research Institute, Medical University of Innsbruck, Austria Received: 10.04.2014 Accepted: 02.07.2014 Published Online: 24.11.2014 Printed: 22.12.2014 Abstract: Glucocorticoids (GCs) induce cell cycle arrest and apoptosis in lymphoid cells and constitute a central component in the treatment of lymphoid malignancies. The molecular basis of this clinically important phenomenon remains, however, poorly understood. Using whole genome expression profiling we have previously identified glucocorticoid response genes in children with acute lymphoblastic leukemia (ALL). The promyelocytic leukemia zinc finger (PLZF) appeared as one of the most promising candidate genes, which has been implicated in the pathogenesis of several leukemia types. We have already established that transgenic PLZF reduced the sensitivity to GC-induced apoptosis in the CEM-C7H2-2C8 leukemic cell line and knockdown of PLZF resulted in a small but significant increase in cell death in this cell line. The present study was proposed to find a plausible molecular explanation for this protective effect of PLZF against GC-induced cell death. It was found that doxycycline-regulated PLZF overexpression in the CCRFCEM T-ALL cell line downregulates the GC-induced GR expression and its target genes, which resulted in reduced apoptosis induced by GC. Key words: PLZF, GR, .
