Ectopic expression of CAAT/enhancer binding protein α (C/EBPα) in p210BCR/ABL-expressing cells induces granulocytic differentiation, inhibits proliferation, and suppresses leukemogenesis. To dissect the molecular mechanisms underlying these biological effects, C/EBPα-regulated genes were identified by microarray analysis in 32D-p210BCR/ABL cells. One of the genes whose expression was activated by C/EBPα in a DNA binding–dependent manner in BCR/ABL-expressing cells is the transcriptional repressor Gfi-1. We show here that C/EBPα interacts with a functional C/EBP binding site in the Gfi-1 5′-flanking region and enhances the promoter activity of Gfi-1. Moreover, in K562 cells, RNA interference–mediated downregulation of Gfi-1 expression partially rescued the proliferation-inhibitory but not the differentiation-inducing effect of C/EBPα. Ectopic expression of wild-type Gfi-1, but not of a transcriptional repressor mutant (Gfi-1P2A), inhibited proliferation and markedly suppressed colony formation but did not induce granulocytic differentiation of BCR/ABL-expressing cells. By contrast, Gfi-1 short hairpin RNA–tranduced CD34+ chronic myeloid leukemia cells were markedly more clonogenic than the scramble-transduced counterpart. Together, these studies indicate that Gfi-1 is a direct target of C/EBPα required for its proliferation and survival-inhibitory effects in BCR/ABL-expressing cells.

Expression of the Transcriptional Repressor Gfi-1 Is Regulated by C/EBP{alpha} and Is Involved in Its Proliferation and Colony Formation-Inhibitory Effects in p210BCR/ABL-Expressing Cells / Lidonnici, Mr; Audia, A; Soliera, Angela Rachele; Prisco, M; Ferrari, Giovanna; Waldron, T; Donato, N; Zhang, Y; Martinez, Rv; Holyoake, Tl; Calabretta, Bruno. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 70:20(2010), pp. 7949-7959. [10.1158/0008-5472.CAN-10-1667]

Expression of the Transcriptional Repressor Gfi-1 Is Regulated by C/EBP{alpha} and Is Involved in Its Proliferation and Colony Formation-Inhibitory Effects in p210BCR/ABL-Expressing Cells.

SOLIERA, Angela Rachele;FERRARI, Giovanna;CALABRETTA, Bruno
2010

Abstract

Ectopic expression of CAAT/enhancer binding protein α (C/EBPα) in p210BCR/ABL-expressing cells induces granulocytic differentiation, inhibits proliferation, and suppresses leukemogenesis. To dissect the molecular mechanisms underlying these biological effects, C/EBPα-regulated genes were identified by microarray analysis in 32D-p210BCR/ABL cells. One of the genes whose expression was activated by C/EBPα in a DNA binding–dependent manner in BCR/ABL-expressing cells is the transcriptional repressor Gfi-1. We show here that C/EBPα interacts with a functional C/EBP binding site in the Gfi-1 5′-flanking region and enhances the promoter activity of Gfi-1. Moreover, in K562 cells, RNA interference–mediated downregulation of Gfi-1 expression partially rescued the proliferation-inhibitory but not the differentiation-inducing effect of C/EBPα. Ectopic expression of wild-type Gfi-1, but not of a transcriptional repressor mutant (Gfi-1P2A), inhibited proliferation and markedly suppressed colony formation but did not induce granulocytic differentiation of BCR/ABL-expressing cells. By contrast, Gfi-1 short hairpin RNA–tranduced CD34+ chronic myeloid leukemia cells were markedly more clonogenic than the scramble-transduced counterpart. Together, these studies indicate that Gfi-1 is a direct target of C/EBPα required for its proliferation and survival-inhibitory effects in BCR/ABL-expressing cells.
2010
70
20
7949
7959
Expression of the Transcriptional Repressor Gfi-1 Is Regulated by C/EBP{alpha} and Is Involved in Its Proliferation and Colony Formation-Inhibitory Effects in p210BCR/ABL-Expressing Cells / Lidonnici, Mr; Audia, A; Soliera, Angela Rachele; Prisco, M; Ferrari, Giovanna; Waldron, T; Donato, N; Zhang, Y; Martinez, Rv; Holyoake, Tl; Calabretta, Bruno. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 70:20(2010), pp. 7949-7959. [10.1158/0008-5472.CAN-10-1667]
Lidonnici, Mr; Audia, A; Soliera, Angela Rachele; Prisco, M; Ferrari, Giovanna; Waldron, T; Donato, N; Zhang, Y; Martinez, Rv; Holyoake, Tl; Calabrett...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/645592
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