Adipocyte Enhancer‐Binding Protein 1 Modulates Adiposity and Energy Homeostasis

Ro, Hyo‐Sung; Zhang, Lei; Majdalawieh, Amin F.; Kim, Sung Woo; Wu, Xue; Lyons, Peter J.; Webber, Chris; Ma, Hong; Reidy, Shannon P.; Boudreau, Aaron; Miller, Jessica R.; Mitchell, Patricia L.; McLeod, Roger S.

doi:10.1038/oby.2007.569

Cited by 38 publications

(47 citation statements)

References 64 publications

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“…They provided evidence that adipocyte enhancer binding protein 1 negatively regulates the PTEN function by protein-protein interaction with PTEN, thus promoting its degradation. In addition, they further suggested that adipocyte enhancer binding protein 1 might be a novel effector of estrogen action that is specific for pathways related to the regulation of obesity (43,44). Their data provide new insights into a further pathway related to the alteration of the PTEN function in overweight and obese women, suggesting a mechanism leading to the inactivation of the tumor suppressor function of PTEN due to increased BMI.…”

Section: Discussionmentioning

confidence: 99%

Combined PTEN and p27kip1 Protein Expression Patterns Are Associated with Obesity and Prognosis in Endometrial Carcinomas

Dellas

Jundt

Sartorius

et al. 2009

Clinical Cancer Research

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Purpose: Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) and p27 kip1 proteins are key players of the Akt pathway, which is nutritionally regulated by insulin receptor signaling and influenced by estrogens. In this study, the prognostic relevance of the PTEN/ p27 kip1 protein expression in endometrial carcinoma in relationship to the body mass index (BMI) was determined. Endometrial cancer represents a major health problem. During the first half of the 20th century, the incidence of cervical cancer was greater than the cancer of the endometrium by a ratio of >3:1, but this trend reversed during the last 50 years (1). Today, endometrial carcinoma is the most common malignant tumor of the female genital tract and the fourth most common cancer in women after carcinomas of the breast, colon, and lung in the western world (2). Epidemiologic data provide a strong link between excess body weight and the risk of developing endometrial carcinoma (3 -6).Endometrial carcinomas are subdivided into two major types based on epidemiology, histopathology, and clinical behavior. Type I tumors are endometrioid endometrial carcinomas (EEC) and type II tumors are non-EEC (NEEC). Type I tumors occur predominantly in perimenopausal women under unopposed estrogenic stimulation. These tumors are frequently preceded by atypical endometrial hyperplasia. They are usually low-grade and confined to the uterus, and most women are cured due to an early detection following the initial symptom of irregular uterine bleeding. In contrast, type II tumors develop mainly in elder women in whom the endometrium is atrophic due to the absence of an estrogenic effect. These tumors are predominantly high-grade serous or clear-cell carcinomas. NEEC invade early into the myometrium. They are aggressive and associated with a less favorable clinical outcome. Whereas EEC are due to increased estrogen hormone levels, mainly in obese, younger patients, NEEC are observed in older patients without increased estrogen levels and without an association with obesity.

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Section: Discussionmentioning

confidence: 99%

Combined PTEN and p27kip1 Protein Expression Patterns Are Associated with Obesity and Prognosis in Endometrial Carcinomas

Dellas

Jundt

Sartorius

et al. 2009

Clinical Cancer Research

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“…Although, we observed enrichment of genes pertaining to activation of NF-kB and PI3Kinase signaling, upon depletion of AEBP1 in U87MG and U138MG cell lines, we did not observe any apparent change in either localization or expression of NFkB (data not shown). Aebp1 is also known to interact with PI3Kinase inhibitor Pten and promote the process of differentiation in preadipocytes (36). PTEN is often deleted in primary GBM, both the cell lines employed in this study were PTEN mutant (data not shown).…”

Section: U87mg U138mgmentioning

confidence: 94%

Identification of Genomic Targets of Transcription Factor Aebp1 and its role in Survival of Glioma Cells

Ladha

Sinha

Bhat

et al. 2012

Molecular Cancer Research

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A recent transcriptome analysis of graded patient glioma samples led to identification of AEBP1 as one of the genes upregulated in majority of the primary GBM as against secondary GBM. Aebp1 is a transcriptional repressor that is involved in adipogenesis. It binds to AE-1 element present in the proximal promoter of aP2 gene that codes for fatty acid binding protein (FABP4). A comprehensive study was undertaken to elucidate the role of AEBP1 overexpression in glioblastoma. We employed complementary gene silencing approach to identify the genes that are perturbed in a glioma cell line (U87MG). A total of 734 genes were differentially regulated under these conditions (≥ 1.5-fold, P ≤ 0.05) belonging to different GO categories such as transcription regulation, cell growth, proliferation, differentiation, and apoptosis of which perturbation of 114 genes of these pathways were validated by quantitative real time PCR (qRT-PCR). This approach was subsequently combined with ChIP-chip technique using an Agilent human promoter tiling array to identify genomic binding loci of Aebp1 protein. A subset of these genes identified for Aebp1 occupancy was also validated by ChIP-PCR. Bioinformatics analysis of the promoters identified by ChIP-chip technique revealed a consensus motif GAAAT present in 66% of the identified genes. This consensus motif was experimentally validated by functional promoter assay using luciferase as the reporter gene. Both cellular proliferation and survival were affected in AEBP1-silenced U87MG and U138MG cell lines and a significant percentage of these cells were directed towards apoptosis.

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“…AEBP1, a transcriptional repressor with carboxypeptidase activity, binds to a regulatory sequence, adipocyte enhancer 1, located in the proximal promoter region of the adipose P2 gene, which encodes the adipocyte fatty acid -binding protein (35). AEBP1 has been shown to interact with the tumor suppressor protein PTEN and inhibit its function, thus promoting cell proliferation (36). Further, AEBP1 levels were found to be higher in proliferative preadipocytes whereas its expression was abolished in terminally differentiated, nonproliferative adipocytes (37).…”

Section: Discussionmentioning

confidence: 99%

Novel Glioblastoma Markers with Diagnostic and Prognostic Value Identified through Transcriptome Analysis

Reddy

Britto²,

Vinnakota³

et al. 2008

Clinical Cancer Research

134

122

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Purpose: Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis. Experimental Design: We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade IIödiffuse astrocytoma, grade IIIöanaplastic astrocytoma, and grade IVöglioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51). Results: We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage^inducible a (GADD45a) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45a and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45a conferred better survival while the coexpression of FSTL1with p53 was associated with poor survival. Conclusions: Our study reveals that GADD45a and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1are primary GBM-specific diagnostic markers. Whereas GADD45a overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM patients.

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Adipocyte Enhancer‐Binding Protein 1 Modulates Adiposity and Energy Homeostasis

Cited by 38 publications

References 64 publications

Combined PTEN and p27kip1 Protein Expression Patterns Are Associated with Obesity and Prognosis in Endometrial Carcinomas

Combined PTEN and p27kip1 Protein Expression Patterns Are Associated with Obesity and Prognosis in Endometrial Carcinomas

Identification of Genomic Targets of Transcription Factor Aebp1 and its role in Survival of Glioma Cells

Novel Glioblastoma Markers with Diagnostic and Prognostic Value Identified through Transcriptome Analysis

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