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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.


ABSTRACT: Ectopic expression of CAAT/enhancer binding protein ? (C/EBP?) in p210BCR/ABL-expressing cells induces granulocytic differentiation, inhibits proliferation, and suppresses leukemogenesis. To dissect the molecular mechanisms underlying these biological effects, C/EBP?-regulated genes were identified by microarray analysis in 32D-p210BCR/ABL cells. One of the genes whose expression was activated by C/EBP? in a DNA binding-dependent manner in BCR/ABL-expressing cells is the transcriptional repressor Gfi-1. We show here that C/EBP? 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/EBP?. 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/EBP? required for its proliferation and survival-inhibitory effects in BCR/ABL-expressing cells.

SUBMITTER: Lidonnici MR 

PROVIDER: S-EPMC2955805 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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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 Maria Rosa MR   Audia Alessandra A   Soliera Angela Rachele AR   Prisco Marco M   Ferrari-Amorotti Giovanna G   Waldron Todd T   Donato Nick N   Zhang Ying Y   Martinez Robert V RV   Holyoake Tessa L TL   Calabretta Bruno B  

Cancer research 20101005 20


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 represso  ...[more]

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