The leukemogenic transcription factor E2a-Pbx1 induces expression of the putative N-myc and p53 target gene NDRG1 in Ba/F3 cells

Rutherford, Michael N.; Bayly, G. R. L.; Matthews, Barbara; Okuda, Tomohiko; Wn, Dinjens; Kondoh, Hisato; LeBrun, David P.

doi:10.1038/sj.leu.2402059

Cited by 22 publications

(17 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of the various suppressor genes linked to the expression of ndrG1/cap43 (40), p53 is known to be closely associated with ndrG1/cap43 in tumor growth and/or cancer cell apoptosis (2,41,42), but the molecular interaction between p53 and ndrG1/cap43 remains unclear. in the present study, we did not examine whether any suppressor gene was linked to ndrG1/cap43 expression in gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Nuclear expression of N-myc downstream regulated gene 1/Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer

Kawahara

Akiba

Hattori

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Expression of n-myc downstream regulated gene 1 (ndrG1)/ca 2+ -associated protein 43 (cap43) in cancer cells is a predictive marker of good or poor prognosis depending on tumor type. in this study, we examined whether ndrG1/ cap43 is a marker of good or poor prognosis in gastric cancer patients, and whether it is associated with tumor stromal responses, including angiogenesis and macrophage infiltration. the expression levels of ndrG1/cap43, the number of cd68-positive macrophages and the cd34-positive microvessel density were analyzed by immunohistochemistry in 129 gastric cancer patients, including 65 with the intestinal type and 64 with the diffuse type. the expression of ndrG1/cap43 in the nucleus and the membrane was evaluated. nuclear ndrG1/ cap43 expression was found in 20/65 (30.8%) patients with the intestinal type and in 9/64 (14.1%) patients with the diffuse type of gastric cancer. nuclear ndrG1/cap43 expression was significantly associated with pathological stage in the intestinal type (p=0.002), but not in the diffuse type (p=0.039). nuclear ndrG1/cap43 expression was also closely associated with infiltrating macrophages (P=0.001) and tumor angiogenesis (p=0.001) in the intestinal type. Furthermore, nuclear ndrG1/cap43 expression was associated with poor prognosis in both the intestinal (p=0.001) and the diffuse types of gastric cancer (p=0.047). By contrast, membranous ndrG1/ cap43 expression was not associated with the overall survival of gastric cancer patients with either the intestinal or diffuse type of gastric cancer. the expression of ndrG1/cap43 in the nucleus may be a predictive biomarker for malignant progression in the intestinal type of gastric cancer, preferable to the expression of ndrG1/cap43 in the membrane.Introduction n-myc downstream regulated gene 1 (ndrG1)/ca 2+ -associated protein 43 (Cap43) has been identified as a nickel-and calciuminduced gene, identical to the homocysteine-inducible gene, reduced in tumor (rtp/rit42) and to the differentiation-related gene-1 (drg-1) (1-6). in cancer progression, overexpression of ndrG1/cap43 was found to reduce cell proliferation and anchorage-independent growth in vitro and tumor growth in vivo (2). however, ndrG1/cap43 has no effect on the primary tumor growth of colon and prostate cancer in vivo (7,8). ndrG1/cap43 expression has been found to be increased in numerous types of human cancer in comparison to normal tissues (8). however, other studies have reported that the expression of ndrG1/cap43 is increased in normal cells and in well-differentiated cancer cells, but decreased in poorly differentiated cancer cells and in cancer of the colon, prostate, breast and pancreas (7-11). this suggests a close association of ndrG1/cap43 with the cancer differentiation status. ndrG1/cap43 is a predictive marker of good prognosis in patients with cancer of the prostate, esophagus, breast, colon and pancreas, and with neuroblastoma (2,8,(12)(13)(14)(15). however, the expression of ndrG1/cap43 is a predictive marker of poor prognosis in pa...

show abstract

Section: Discussionmentioning

confidence: 99%

Nuclear expression of N-myc downstream regulated gene 1/Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer

Kawahara

Akiba

Hattori

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…The medium contained G418 (1.2 mg/ml) in the first plating only. Cell cycle analysis by flow cytometry was carried out as described previously (25).…”

Section: Methodsmentioning

confidence: 99%

E2A-PBX1 Interacts Directly with the KIX Domain of CBP/p300 in the Induction of Proliferation in Primary Hematopoietic Cells

Bayly

Chuen

Currie

et al. 2004

Journal of Biological Chemistry

106

View full text Add to dashboard Cite

The E2A gene encodes DNA-binding transcription factors, called E12 and E47, involved in cell specification and maturation. E2A is also involved in a chromosomal translocation that leads to the expression of an oncogenic transcription factor called E2A-PBX1 in cases of acute leukemia. In the work described here, we elucidate the interaction between E2A-PBX1 and transcriptional co-activators. We confirm that the E2A portion can interact with CBP and PCAF and map required elements on E2A and CBP. On CBP, the interaction involves the KIX domain, a well characterized domain that mediates interactions with several other oncogenic transcription factors. On E2A, the interaction with CBP requires conserved ␣-helical domains that reside within activation domains 1 and 2 (AD1 and AD2, respectively). Using purified, recombinant proteins, we show that the E2A-CBP interaction is direct. Notwithstanding the previously demonstrated ability of AD1 and AD2 to function independently, some of our findings suggest functional cooperativity between these two domains. Finally, we show that the CBP/p300-interactive helical domains of E2A are important in the induction of proliferation in cultured primary bone marrow cells retrovirally transduced with E2A-PBX1. Our findings suggest that some aspects of E2A-PBX1 oncogenesis involve a direct interaction with the KIX domain of CBP/p300.

show abstract

“…E2a-Pbx1 is a fusion protein of transcription factors E2a and Pbx1 generated by chromosomal translocation that possibly causes pediatric acute lymphoblastic leukemia (45). Enforced expression of E2a-Pbx1 induced the expression of endogenous Drg-1 and activated the Drg-1 promoter-mediated reporter activity (46). In contrast to the transcription factors p53, HIF-1, c-Jun/AP-1, and E2a-Pbx1, the transcription factors N-Myc and c-Myc were found to suppress the expression of Drg-1 by corroboration with Max (29).…”

Section: Comparison Of the Effects Of Mimosine On Drg-1 Expression Wimentioning

confidence: 99%

Modulation of Differentiation-related Gene 1 Expression by Cell Cycle Blocker Mimosine, Revealed by Proteomic Analysis

Dong

Arnold

Yang

et al. 2005

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

L-Mimosine, a plant amino acid, can reversibly block mammalian cells at late G 1 phase and has been found to affect translation of mRNAs of the cyclin-dependent kinase inhibitor p27, eIF3a (eIF3 p170), and ribonucleotide reductase M2. The effect of mimosine on the expression of these genes may be essential for the G 1 phase arrest. To determine additional genes that may be early respondents to the mimosine treatment, we performed two-dimensional gel electrophoretic analysis of [35 S]methionine-labeled cell lysates followed by identification of the altered protein spots by LC-tandem mass spectrometry. In this study, the synthesis of two protein spots (MIP42 and MIP17) was found to be enhanced by mimosine, whereas the formation of another protein spot (MSP17) was severely blocked following mimosine treatment. These protein spots, MIP42, MIP17, and MSP17, were identified to be differentiation-related gene 1 (Drg-1; also called RTP, cap43, rit42, Ndrg-1, and PROXY-1), deoxyhypusine-containing eIF5A intermediate, and mature hypusine-containing eIF5A, respectively. The effect of mimosine on eIF5A maturation was due to inhibition of deoxyhypusine hydroxylase, the enzyme catalyzing the final step of hypusine biosynthesis in eIF5A. The mimosine-induced expression of Drg-1 was mainly attributable to increased transcription likely by the c-Jun/AP-1 transcription factor. Because induction of Drg-1 is an early event after mimosine treatment and is observed before a notable reduction in the steady-state level of mature eIF5A, eIF5A does not appear to be involved in the modulation of Drg-1 expression. Molecular & Cellular Proteomics 4:993-1001, 2005.

show abstract

The leukemogenic transcription factor E2a-Pbx1 induces expression of the putative N-myc and p53 target gene NDRG1 in Ba/F3 cells

Cited by 22 publications

References 37 publications

Nuclear expression of N-myc downstream regulated gene 1/Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer

Nuclear expression of N-myc downstream regulated gene 1/Ca2+-associated protein 43 is closely correlated with tumor angiogenesis and poor survival in patients with gastric cancer

E2A-PBX1 Interacts Directly with the KIX Domain of CBP/p300 in the Induction of Proliferation in Primary Hematopoietic Cells

Modulation of Differentiation-related Gene 1 Expression by Cell Cycle Blocker Mimosine, Revealed by Proteomic Analysis

Contact Info

Product

Resources

About