The Role of CREB as a Proto-oncogene in Hematopoiesis

Kinjo, Kozen; Sandoval, Salemiz; Sakamoto, Kathleen M.; Shankar, Deepa B.

doi:10.4161/cc.4.9.1991

Cited by 51 publications

(52 citation statements)

References 14 publications

(20 reference statements)

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“…CREB is a member of the activating transcription factor/CREB family of transcription factors, which can regulate diverse cellular responses, including proliferation, survival, and differentiation (25)(26)(27). For instance, CREB has been reported to be a proto-oncogene, leading to increased proliferation of myeloid cells and myeloproliferative diseases (46,47). In the present study, we excitingly found that CREB level was downregulated in MDSCs after WGP treatment, which was dectin-1-dependent.…”

Section: Discussionsupporting

confidence: 58%

MicroRNA-9 Regulates the Differentiation and Function of Myeloid-Derived Suppressor Cells via Targeting Runx1

Tian

Rui

Tang

et al. 2015

The Journal of Immunology

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Myeloid-derived suppressor cells (MDSCs) play a critical role in tumor-associated immunosuppression, thus affecting effective immunotherapies for cancers. However, the molecular mechanisms involved in regulating the differentiation and function of MDSCs remain largely unclear. In this study, we found that inhibition of microRNA (miR)-9 promoted the differentiation of MDSCs with significantly reduced immunosuppressive function whereas overexpression of miR-9 markedly enhanced the function of MDSCs. Notably, knockdown of miR-9 significantly impaired the activity of MDSCs and inhibited the tumor growth of Lewis lung carcinoma in mice. Moreover, miR-9 regulated MDSCs differentiation by targeting the runt-related transcription factor 1, an essential transcription factor in regulating MDSC differentiation and function. Furthermore, the CREB was found to regulate miR-9 expression in MDSCs. Taken together, our findings have identified a critical role of miR-9 in regulating the differentiation and function of MDSCs.

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Section: Discussionsupporting

confidence: 58%

MicroRNA-9 Regulates the Differentiation and Function of Myeloid-Derived Suppressor Cells via Targeting Runx1

Tian

Rui

Tang

et al. 2015

The Journal of Immunology

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“…Kinjo et al reported that a majority of patients with acute lymphoid and myeloid leukemia overexpressed CREB in the bone marrow. CREB overexpression was associated with poor initial outcome of clinical disease in patients with acute myelocytic leukemia (21). Our study proved that CREB5 was significantly overexpressed in epithelial ovarian cancer.…”

Section: Discussionmentioning

confidence: 50%

CREB5 promotes tumor cell invasion and correlates with poor prognosis in epithelial ovarian cancer

Deng

Liao

et al. 2017

Oncol Lett

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Abstract. CAMP responsive element binding protein 5 (CREB5) has crucial roles in regulating cell growth, proliferation, differentiation and cell cycle regulation. CREB5 has been identified to be overexpressed in several types of human cancer. However, the expression characteristics of CREB5 in epithelial ovarian cancer remains unknown, and its potential clinical prognostic significance has not yet been elucidated. In the present study, quantitative polymerase chain reaction (qPCR) and western blot analysis were performed to detect CREB5 mRNA and protein expression levels in 10 fresh tissue and cell lines epithelial ovarian cancer. Furthermore, CREB5 expression was analyzed using immunohistochemical analysis in 125 clinicopathologically characterized ovarian cancers: Stage I+II (n=31), stage III (n=70), stage IV (n=24). The patient survival rate was evaluated using Kaplan-Meier analysis. CREB5 was significantly overexpressed at both the mRNA and protein levels in epithelial ovarian cancer cells. There was a significant positive correlation between high CREB5 expression and increasing the International Federation of Gynecology and Obstetrics (FIGO) stage and pelvic lymph node metastasis (P<0.05). Patients with high CREB5 expression had a shorter overall survival, whereas patients with low CREB5 expression had longer survival. In addition, patients with high CREB5 expression had shorter relapse-free survival whereas patients with low CREB5 expression had longer relapse-free survival. Univariate logistic regression analysis and stepwise multivariate analysis all revealed that the FIGO stage and high CREB5 expression were significant risk factors for epithelial ovarian cancer (P<0.001), which suggested that CREB5 upregulation may be associated with a poor prognosis; therefore, it may be an independent prognostic indicator of epithelial ovarian cancer and may serve as a tumor-aggressive gene.

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“…Acute myeloid leukemia is an aggressive, heterogeneous disease with numerous cytogenetic abnormalities and mutations within key signaling pathways involved in cell differentiation, proliferation, and survival (Van Etten, 2007). These key signaling molecules include the PI3K/Akt signaling network (Martelli et al, 2007), RAS signaling pathways (Flotho et al, 2007), Wnt signaling (Mikesch et al, 2007), transforming growth factor-␤ (Lin et al, 2005), FLT-3 (Markovic et al, 2005), Cotylenin A (Honma, 2002), cAMP response element-binding protein (Kinjo et al, 2005), EGFR (Bacchiocchi et al, 2005;Nishioka et al, 2010), JNK (Lagadinou et al, 2008), and AMPK (Campà s et al, 2003;Drakos et al, 2009). Considering these complex signaling events, we hypothesized that CYP2J2-derived EETs may participate in hematological malignant diseases through one or more of these pathways.…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 2J2 Is Highly Expressed in Hematologic Malignant Diseases and Promotes Tumor Cell Growth

Chen

Wei²,

Rao³

et al. 2010

J Pharmacol Exp Ther

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Cytochrome P450 2J2 (CYP2J2) epoxygenase converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs) that exert multiple biological effects in the cardiovascular system and in various human solid cancers. However, it is unknown whether this enzyme is expressed or plays any role in malignant hematological diseases. In this study, we found strong and highly selective CYP2J2 expression in five human-derived malignant hematological cell lines and in leukemia cells from peripheral blood and bone marrow in 36 of 42 patients (86%) with malignant hematologic diseases. Furthermore, increased levels of EETs were detected in urine and blood samples from these patients. Addition of exogenous EET or CYP2J2 overexpression in cultured human-derived malignant hematologic cell lines markedly accelerated proliferation and attenuated apoptosis. Addition of the selective CYP2J2 inhibitor compound 26 (C26; 1-[4-(vinyl) phenyl]-4-[4-(diphenyl-hydroxymethyl)-piperidinyl]-butanone hydrochloride) inhibited cell proliferation and increased apoptosis, an effect that was significantly reversed by EET. CYP2J2 overexpression and exogenous EET activated AMP-activated protein kinase, c-Jun NH 2 -terminal kinase, and phosphatidylinositol 3-kinase/Akt signaling pathways, and increased epidermal growth factor receptor phosphorylation levels. CYP2J2 overexpression also enhanced malignant xenograft growth, which was efficiently inhibited by oral administration of C26 in Tie2-CYP2J2 transgenic mice and in severe combined immunodeficiency (SCID) xenograft mice. Together, these results suggest that CYP2J2 plays a key role in the pathogenesis of human hematologic malignant diseases. Selective inhibition of CYP2J2 may be a promising therapeutic strategy for these conditions.

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The Role of CREB as a Proto-oncogene in Hematopoiesis

Cited by 51 publications

References 14 publications

MicroRNA-9 Regulates the Differentiation and Function of Myeloid-Derived Suppressor Cells via Targeting Runx1

MicroRNA-9 Regulates the Differentiation and Function of Myeloid-Derived Suppressor Cells via Targeting Runx1

CREB5 promotes tumor cell invasion and correlates with poor prognosis in epithelial ovarian cancer

Cytochrome P450 2J2 Is Highly Expressed in Hematologic Malignant Diseases and Promotes Tumor Cell Growth

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