Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells

Shimabe, Munetake; Goyama, Susumu; Watanabe‐Okochi, Naoko; Yoshimi, Akihide; Ichikawa, Motoshi; Imai, Yumiko; Kurokawa, Mineo

doi:10.1038/onc.2009.288

Cited by 64 publications

(53 citation statements)

References 47 publications

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“…EVI-1 induces PBX1, one of the major stemness-associated gene (Shimabe et al, 2009). Therefore, reduced miR-22 expression in metastatic cells may lead to elevated expression of stemness-associated genes.…”

Section: Discussionmentioning

confidence: 99%

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

et al. 2010

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Metastasis in breast cancer carries a disproportionately worse prognosis than localized primary disease. To identify microRNAs (miRNA) involved in metastasis, the expression of 254 miRNAs was measured across the following cell lines using microarray analysis: MDA-MB-231 breast cancer cells, cells that grew as a tumor in the mammary fat pad of nude mice (TMD-231), metastatic disease to the lungs (LMD-231), bone (BMD-231) and adrenal gland (ADMD-231). A brain-seeking variant of this cell line (231-BR) was used additionally in validation studies. Twenty miRNAs were upregulated and seven were downregulated in metastatic cancer cells compared with TMD-231 cells. The expression of the tumor suppressor miRNAs let-7 and miR-22 was consistently downregulated in metastatic cancer cells. These metastatic cells expressed higher levels of putative/proven miR-22 target oncogenes ERBB3, CDC25C and EVI-1. Introduction of miR-22 into cancer cells reduced the levels of ERBB3 and EVI-1 as well as phospho-AKT, an EVI-1 downstream target. The miR-22 primary transcript is located in the 5 0 -untranslated region of an open reading frame C17orf91, and the promoter/enhancer of C17orf91 drives miR-22 expression. We observed elevated C17orf91 expression in non-basal subtype compared with basal subtype breast cancers. In contrast, elevated expression of EVI-1 was observed in basal subtype and was associated with poor outcome in estrogen receptor-negative breast cancer patients. These results suggest that metastatic cancer cells increase specific oncogenic signaling proteins through downregulation of miRNAs. Identifying such metastasisspecific oncogenic pathways may help to manipulate tumor behavior and aid in the design of more effective targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

et al. 2010

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“…33,34 Moreover, recent analysis of the Pbx1 promoter region in mice revealed that Evi-1 upregulates Pbx1 transcription. 50 This emphasizes that PBX1 is a possible target gene of EVI1 involved in the leukemogenesis of EVI1 þ patients. Although differences in EFS and OS for EVI1 þ and EVI1À pediatric AML were observed in our study, we showed that EVI1 þ has no independent prognostic value for pediatric AML, which is in contrast to adult AML.…”

Section: Discussionmentioning

confidence: 99%

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

et al. 2010

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Overexpression of the ecotropic virus integration-1 (EVI1) gene (EVI1 þ ), localized at chromosome 3q26, is associated with adverse outcome in adult acute myeloid leukemia (AML). In pediatric AML, 3q26 abnormalities are rare, and the role of EVI1 is unknown. We studied 228 pediatric AML samples for EVI1 þ using gene expression profiling and RQ-PCR. EVI1 þ was found in 20/213 (9%) of children with de novo AML, and in 4/8 with secondary AML. It was predominantly found in MLLrearranged AML (13/47), monosomy 7 (2/3), or FAB M6/7 (6/10), and mutually exclusive with core-binding factor AML, t(15;17), and NPM1 mutations. Fluorescent in situ hybridization (FISH) was performed to detect cryptic 3q26 abnormalities. However, none of the EVI1 þ patients harbored structural 3q26 alterations. Although significant differences in 4 years pEFS for EVI1 þ and EVI1À pediatric AML were observed (28%±11 vs 44%±4, P ¼ 0.04), multivariate analysis did not identify EVI1 þ as an independent prognostic factor. We conclude that EVI1 þ can be found in B10% of pediatric AML. Although EVI1 þ was not an independent prognostic factor, it was predominantly found in subtypes of pediatric AML that are related with an intermediate to unfavorable prognosis. Further research should explain the role of EVI1 þ in disease biology in these cases. Remarkably, no 3q26 abnormalities were identified in EVI1 þ pediatric AML.

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“…However, transcriptome examination of Prdm3 mutant and Prdm16 mutant HSCs suggests they are regulating somewhat different programs (Aguilo et al, 2011). For example, Prdm3 promotes Pbx1 expression, whereas Prdm16 may repress it (Aguilo et al, 2011;Goyama et al, 2008;Shimabe et al, 2009). Interestingly, Prdm16, but not Prdm3, also maintains embryonic cortical stem cells, and this occurs in part through regulating oxidative stress (Chuikov et al, 2010;Kinameri et al, 2008).…”

Section: Prdms In Haematopoietic Stem Cellsmentioning

confidence: 99%

“…Prdm3 may have a similar mode of action at the Pbx1 (pre-B-cell leukaemia homeobox 1) locus (Shimabe et al, 2009), and Prdm8 at the Cdh11 (cadherin 11) locus (Ross et al, 2012). Prdm8 is expressed in several regions of the developing nervous system (Table 2) (Kinameri et al, 2008;Komai et al, 2009) and is coexpressed in several places with the DNA sequence-specific bHLH (basic helix-loop-helix) transcription factor Bhlhb5 (Bhlhe22 -Mouse Genome Informatics) (Ross et al, 2012).…”

Section: Sequence-specific Targeting Of Prdms Through Complex Formationmentioning

confidence: 99%

The Prdm family: expanding roles in stem cells and development

2012

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SummaryMembers of the Prdm family are characterized by an Nterminal PR domain that is related to the SET methyltransferase domain, and multiple zinc fingers that mediate sequence-specific DNA binding and protein-protein interactions. Prdm factors either act as direct histone methyltransferases or recruit a suite of histone-modifying enzymes to target promoters. In this way, they function in many developmental contexts to drive and maintain cell state transitions and to modify the activity of developmental signalling pathways. Here, we provide an overview of the structure and function of Prdm family members and discuss the roles played by these proteins in stem cells and throughout development.

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Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells

Cited by 64 publications

References 47 publications

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

The Prdm family: expanding roles in stem cells and development

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