bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-272: A novel isoform of Sox5 is expressed in TRAF3-deficient mouse B lymphomas
Authors: Edwards Shanique K.E. , Desai Anand , Moore Carissa R. , Liu Yan , Hart Ronald P. , Xie Ping 
Published: August 2012

Abstract
TRAF3 is a novel tumor suppressor identified in human non-Hodgkin lymphoma and multiple myeloma. We recently reported that TRAF3 deletion causes vastly prolonged survival of mature B cells, which eventually leads to B lymphoma development in mice. The long latency of B lymphoma development observed in B-TRAF3−/− mice suggest that additional oncogenic pathways are required for B lymphomagenesis. To delineate such oncogenic pathways in TRAF3−/− B lymphomas, we performed microarray analyses and identified Sox5 as a gene recurrently up-regulated in B lymphomas spontaneously developed in different individual B-TRAF3−/− mice. We confirmed the striking up-regulation of Sox5 expression in TRAF3−/− B lymphomas at both the mRNA and protein levels by quantitative real time PCR and Western blot analyses, respectively. We further cloned the full-length cDNA of Sox5 from B lymphomas derived from 4 different individual B-TRAF3−/− mice. Surprisingly, we found that the sequence of Sox5 expressed in TRAF3−/− B lymphomas represents a novel isoform of Sox5, which has not been previously reported. This new isoform of Sox5 contains a 35 aa deletion in the N-terminal region in front of the leucine zipper domain. When transduced into human multiple myeloma cells, the cloned Sox5 cDNA was expressed into a protein of 80 kDa, a size identical to that detected in TRAF3−/− B lymphomas. Taken together, our findings identified a novel isoform of Sox5 as a candidate oncogene in B lymphoma. Our ongoing experiments will further elucidate the roles and mechanisms of Sox5 in TRAF3 deficiency-initiated B cell malignant transformation. This study is supported by a seed grant from the New Jersey Commission on Cancer Research (10-1066-CCR-EO, P. Xie), a Faculty Research Grant (P. Xie), and the Arthur Herrmann Endowed Cancer Research Fund (P. Xie); supported in part by a grant from NCI (R. Hart) and an Aresty Research Grant (A. Desai).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-272. doi:1538-7445.AM2012-LB-272
Abstract LB-275: Genome-wide analysis of the vitamin D receptor (VDR) binding sites reveals vitamin D role mediating autophagy in luminal-like breast cancer cells
Authors: Tavera Luz E. , Westerling Thomas , Brown Myles 
Published: August 2012

Abstract
The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), regulates gene expression through the vitamin D receptor (VDR). Even though 1,25D3 is still best known as a regulator of bodily calcium homeostasis, 1,25D3 has a plethora of physiological actions which include immune and nervous system modulation, cellular proliferation and differentiation. Epidemiological and model studies have revealed the cancer-protective properties of 1,25D3 in colon, prostate and notably in breast. We are actively investigating the anti-proliferative properties of 1,25D3 in a panel of human breast cancer cell lines. We found that 1,25D3 induces autophagy in several luminal-like breast cancer cell models, but not in basal-like or mesenchymal-like models. We performed VDR and signaling partner RXR whole-genome ChIP-seq analysis to uncover all of the direct 1,25D3 target genes involved in regulation of metabolism and autophagy. Our preliminary studies suggest that energy regulation as an important aspect of 1,25D3 anti-proliferative properties in luminal-like breast cancer cells
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-275. doi:1538-7445.AM2012-LB-275
Abstract LB-276: 2-D DIGE and siRNA to find new cancer targets
Authors: Jorsback Anneli , Winkvist Maria , Hagner-McWhirter Åsa , Landström Marene , Sundar Reshma , Engström Ulla 
Published: August 2012

Abstract
siRNA is a powerful tool in loss-of-function studies which generates valuable information on target validation. siRNA is highly selective and suppress gene expression in a sequence-specific manner. These features have made it a key tool in signal transduction - a cornerstone in cancer biology. 2-D DIGE (two dimensional differential gel electrophoresis) is a fluorescence based technology with the capacity to separate thousands of proteins in one single run, with high reproducibility. This makes it a valuable tool for differential expression analyses. In this study two powerful methods, siRNA and 2-D DIGE, were combined to investigate a well-known signaling pathway, pivotal in cancer biology. Silencing of the target protein made it possible not only to identify a large number of proteins that were differentially regulated but also to resolve the time dependency of protein regulation. Thus the combined use of siRNA and 2-D DIGE made it possible to find potentially new targets in the signaling pathway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-276. doi:1538-7445.AM2012-LB-276
Abstract LB-277: Global translational regulation by miR-520c
Authors: Mazan-Mamczarz Krystyna , Zhao Frank , Dai Bojie , Steinhardt James , Gartenhaus Ronald B. 
Published: August 2012

Abstract
MicroRNAs (miRNAs) are endogenous small non-protein-coding RNAs that control a variety of cellular processes by modulating protein expression. Many studies have focused on the role of microRNAs in cancer development and age-related diseases, but the cellular mechanisms by which microRNAs influence aberrant cell growth are still poorly understood. We found that overexpression of a miR-520c-3p precursor decreased global gene translation, and induced senescence as measured by monitoring beta-galactosidase activity and other senescence markers. To better understand the mechanisms underlying miR-520c-3p mediated global translational repression, we performed translational profiling of mRNA isolated from polysomal fractions. We identified subsets of cancer-related genes with repressed translation after overexpression of miR-520c-3p. Interestingly, among them we found eukaryotic translation initiation factor 4 gamma 3 (eIF4G3), a key component of the cap-dependent translation regulation complex (eIF4F). While increases in miR-520c-3p did not change eIF4G3 mRNA abundance, there was a significant reduction in eIF4G3 protein synthesis. The specific repressive influence of miR-520c-3p on eIF4G3 was confirmed by employing heterologous reporter constructs bearing the 3′ untranslated region (3′UTR) of eIF4G3 mRNA. In addition, either miR-520c-3p overexpression or eIF4G3 knockdown, led to decreased eIF4E association with the translation initiation complex as measured by 7-methyl-GTP cap analog pull down, and diminished colony formation in lymphoma cells, as assessed by clonogenic assays. Finally, our findings that, diffuse large B cell lymphoma (DLBCL) cells express low levels of miR-520c-3p with reciprocally high eIF4G3 protein levels, and that TMA analysis revealed significantly higher eIF4G3 expression in patient DLBCL samples compared to normal GCB cells, supports the role of these molecules in the dysregulation of protein synthesis present in NHL. In summary, we demonstrated that overexpression of mir-520c-3p can suppress tumor growth by decreasing global protein translation and inducing senescence in DLBCL cells, and that miR-520c-3p elicits these actions by repressing eIF4G3 expression. Repressed global gene translation and premature senescence blocks cell proliferation, and together function as tumor suppressor mechanisms. Therefore, inhibition of translation and induction of senescence by miRNAs and/or small molecule inhibitors that target eIF4G3 is an innovative strategy for lymphoma therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-277. doi:1538-7445.AM2012-LB-277
Abstract LB-279: SIRT6 expression is regulated by cAMP signaling system in non small cell lung cancer cells
Authors: Kim Eui-Jun , Juhnn Yong-Sung 
Published: August 2012

Abstract
Sirtuin 6 (SIRT6) is a member of the NAD+ dependent histone deacetylase (HDAC) family. HDACs play an important role in epigenetic regulation of gene expression, which is counteracted by histone acetyl-transferase (HAT). HDACs remove acetyl-group at lysine residue of histone tail, and change the conformation of chromatin complex, which eventually regulates transcription activity in of various cancer cells. SIRT6 is reported to be a site specific deacetylase acting at histone H3K9 and H3K56, but very few studies on the regulation of SIRT6 expression have been reported. Cyclic AMP (cAMP) signaling system regulates a variety of cellular responses including metabolism, gene expression, proliferation and death. Therefore, we studied the effect of cAMP signaling system on the expression of SIRT6 and its underlying mechanism in lung cancer cells. Stimulatory heterotrimeric GTP-binding proteins (Gαs) are activated by various ligand-bound receptors and stimulate adenylate cyclase to activate cAMP signaling system. Expression of constitutive active Gαs (GαsQL) decreased SIRT6 protein level without change in its mRNA level in H1299 lung cancer cells. GαsQL expression accelerated proteasomal degradation of SIRT6, resulting in a decreased half-life of the protein from 2.2 h to 1.2 h. SIRT6 expression was also decreased by forskolin (adenylate cyclase activator), but increased by H89 (PKA inhibitor). These results indicate that cAMP signaling system decreases SIRT6 expression by accelerating proteasomal degradation of SIRT6 expression via PKA-dependent pathway in lung cancer cells. This finding suggests that cAMP signaling system can contribute epigenetic regulation of cancer-related gene expression by modifying SIRT6 expression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-279. doi:1538-7445.AM2012-LB-279
Abstract LB-28: A co-op of EGFR and EphA4 promotes the progression of NSCLC through EGF-Grb7-Stat3 mediated transcriptional regulation of EphA4 gene expression
Authors: Chu Pei-Yu , Li Tsai-Kun , Chou Kai-Ming , Shen Tang-Long 
Published: August 2012

Abstract
Growth factor receptor bound protein-7 (Grb7) regulates diverse cellular functions as a result of its multi-domain functionality in protein-protein interactions. A number of reports have indicated that Grb7 is essential for EGFR-mediated tumorigenesis and cancer progression. However, it remains unclear how Grb7 potentiates tumor progression. To understand the underlying mechanisms by which Grb7 participates in EGFR-mediated tumorigenesis, we utilized microarray analyses and yeast two-hybrid screening to explore Grb7-mediated signaling. Of which, a migration related protein, EphA4, was markedly up-regulated in associated with Grb7 overexpression but down-regulated while knocking down Grb7. Eventually, in response to EGF stimulation, we found that Grb7 was trans-located into the nucleus from the cytoplasm, which in turn promoted STAT3 transcriptional activity on EphA4 gene expression. The significance of this finding is further highlighted by the co-upregulation of Grb7 and EphA4 is concurrent with the highly invasive capability of lung adenocarcinoma. Moreover, we found that EphA4 could also potentiate EGF-induced reorganization of cytoskeleton, ERK1/2 phosphorylation, and cancer cell functions such as proliferation, migration and anchorage-independent growth. Based on these findings, we hypothesize that EphA4 can act as an amplifier involved EGF-mediated cancer progression in an EGF/Grb7/Stat3-mediated transcriptional manner. This study reveals a novel mechanism by which Grb7 regulates tumor progression through the EGF- by triggering EphA4 expression and then prolonging EGFR signaling in regulation of diverse cellular functions involved in cancer progression, thereby highlighting the potential strategy to target Grb7 for anti-cancer therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-28. doi:1538-7445.AM2012-LB-28
Abstract LB-280: RNP biogenesis factor Thoc1 is targeted for ubiquitination by NEDD4-1 E3 ligase
Authors: Song Fei , Fan Chuandong , Zhang Xiaojing , Wang Xinjiang , Goodrich David W. 
Published: August 2012

Abstract
Thoc1 encodes an essential protein component (pThoc1) of the THO complex that regulates the packaging of nascent transcripts into ribonucleoprotein complexes (RNPs). Loss of pThoc1 compromises transcriptional elongation, RNA processing, and RNA export. Up-regulation of pThoc1 expression is common in a number of different cancers relative to normal tissue (Guo et al., 2005, Yang et al., 2008) and Thoc1 is preferentially required by neoplastic cells for growth and viability (Li et al., 2007). It is unclear how Thoc1 protein or the THO complex is normally regulated. In this study we examined whether pThoc1 is modified and regulated by ubiquitination because it is a low abundant protein in normal tissue. We found that both endogenous and ectopically expressed pThoc1 are polyubiquitinylated in Hela cells. Importantly, we identified that NEDD4-1 (neural precursor cell expressed developmentally down-regulated protein 4) is an E3 ligase that can mediate pThoc1 ubiquitination. This conclusion was reached based on several lines of evidence. First, overexpression of wild type but not the enzyme-dead NEDD4-1 increased pThoc1 ubiquitination. Second, pThoc1 ubiquitination was significantly reduced in Nedd4 knock out murine embryonic fibroblasts (MEFs) compared to the wild type MEFs. Third, inducible knockdown of NEDD4-1 expression in HeLa cells caused significant reduction in pThoc1 ubiquitination. These results indicate that pThoc1 is a novel substrate of NEDD4-1 E3 ligase in cells. Regulation of pThoc1 functions by NEDD4-1 mediated ubiquitination merits further investigation. This study was supported by grant # NIH R01 CA125665
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-280. doi:1538-7445.AM2012-LB-280
Abstract LB-282: Myxovirus (influenza virus) resistance 1 (MX1) polymorphism in prostate cancer
Authors: Glymph Shanora , Mandal Sanjay , Evans Ashley , Chaudhary Jaideep 
Published: August 2012

Abstract
PURPOSE: Myxovirus (influenza virus) resistance 1 (MX1) is an interferon regulated gene responsible for a specific antiviral state against viral infection. We have previously shown that MX1 is up-regulated by androgens in the normal prostate epithelial cells; however, there is no known role for MX1 in cancer. Meta-analysis of different expression databases e.g. NCBI GEO and Oncomine suggested a strong inverse association between MX1 expression and prostate cancer. To confirm these studies, we performed Immunohistochemistry on normal prostate and prostate cancer tissues. Our data revealed that MX1 expression was indeed decreased in PCa as compared to normal, indicating that MX1 could be transcriptionally down-regulated. Literature studies indicated that MX1 down-regulation could be due to a specific polymorphism in the proximal MX1 promoter. In the promoter region of MX1 at position -88, a single nucleotide polymorphism G&gt;T (rs2071430) is involved in modifying the gene expression. Interestingly, the rs2071430 harbors an interferon-stimulated response element (ISRE) that is required for MX1 expression in response to interferons. The “T” allele restores whereas the “G” allele attenuates ISRE binding resulting in increased or decreased MX1 expression respectively. Based on these observations we hypothesized that decreased expression of MX1 in prostate cancer could be due to the rs2071430 polymorphism. DESIGN METHODS: We investigated MX1 rs2071430 polymorphism in genomic DNA from equal number of disease free and prostate cancer samples (N=305). The sample size required to achieve statistically significant associations were calculated using the power calculator for case control genetic association studies. Polymorphism was detected by sequencing the PCR amplicon through SNPdetector to ensure that the SNP was due to heterozygous allelic variations and not due to sequencing artifacts. RESULTS: The data suggests that the GG genotype (low promoter activity) is higher in PCa (72%) as compared to normal (58.6%). The TT genotype (high activity) was higher in normal (5.7%) compared to PCa (2.4%). No TT genotype was observed in Caucasian normal samples. The results were statistically significant at P&lt;0.05. Our results, for the first time demonstrate that MX1 is down-regulated in prostate cancer possibly at the transcriptional level due to ISRE polymorphism in the promoter region. ACKNOWLEDGEMENTS: This research is supported by NIH/NCMHD grant 1P20MD002285-01.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-282. doi:1538-7445.AM2012-LB-282
Abstract LB-286: 3p24 tumor suppressor gene RBMS3 in NPC
Authors: Chen Juan 
Published: August 2012

Abstract
Deletion within the 3p chromosomal region are one of the most frequent genetic alterations in many solid tumors, including nasopharyngeal carcinoma (NPC), suggesting the existence of one or more tumor suppressor genes (TSGs) within the frequently deleted region. A putative TSG RBMS3, located at the frequently deleted region 3p24-p23, has been identified in our previous study. Here, we reported that down-regulation of RBMS3 was detected in 3/3 (100%) NPC cell lines and 13/15 (86.7%) primary NPC tissues. Functional analysis demonstrated that RBMS3 was able to suppress tumorigenicity of NPC cells both in vitro and in vivo, including inhibiting the cell growth rate, colony formation in vitro and tumor formation in nude mice. Additionally, the tumor suppressive mechanism of RBMS3 was associated with its role in cell cycle arrest at the G1/S checkpoint by the up-regulation of p53, and p21, the down-regulation of Smad4, cyclin D1, cyclin E/CDK2, and the subsequent inhibition of Rb-ser780. Further analysis demonstrated that RBMS3 had a pro-apoptotic role in a mitochondrial-dependent manner via activation of caspase-9 and PARP. Finally, RBMS3 inhibited microvessel formation, which may be mediated by down-regulation of β-catenin and inactivation of its downstream targets, including c-Myc, MMP7, MMP9, and MMP2. Taken together, our findings define a function for RBMS3 as an important tumor suppressor gene in NPC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-286. doi:1538-7445.AM2012-LB-286
Abstract LB-287: TPX2 acts as a scaffold and co-activator protein for the oncogenic kinase Aurora B
Authors: Iyer Jyoti , Tsai Ming-Ying 
Published: August 2012

Abstract
Aurora B kinase is a master regulator of mitosis and is over-expressed in a variety of malignancies including astrocytomas, seminomas, ependymomas, prostate cancer and non small-cell lung cancer. Several Aurora B inhibitors are currently being evaluated for their efficacy in cancer therapy. Therefore, it is critical to understand the regulation of Aurora B activity by other proteins. Aurora B forms the enzymatic core of the Chromosomal Passenger Complex (CPC). The CPC consists of three other proteins besides Aurora B: INCENP, Survivin and Borealin. All these proteins have been known to promote Aurora B activation. The mitotic protein Targeting Protein for Xenopus kinesin-like protein 2 (TPX2) co-localizes with Aurora B at several stages of mitosis, hinting at the existence of a signaling cross-talk between Aurora B and TPX2. The main purpose of our study is to determine whether Aurora B and TPX2 can cross-talk with each other during mitosis, and if found so, to decode the mechanism by which this signaling cross-talk occurs. We hypothesize that TPX2 can transmit signals to regulate Aurora B activity during mitosis. To test our hypothesis, we have performed experiments utilizing M-phase Xenopus egg extracts (XEE) which possess an abundance of mitotic proteins, and human cell lines as model systems. By performing immunoprecipitation assays (IPs) in M-phase XEE, we detected an interaction between TPX2 and the CPC proteins - Aurora B, INCENP and Survivin. This validates the existence of a signaling cross-talk between TPX2 and the CPC proteins. Moreover, IPs and microtubule pelleting assays utilizing XEE revealed that, as is typical of scaffold proteins, either too much or too little TPX2 alters Aurora B activity. Significantly, immunodepletion of endogenous TPX2 from XEE decreases the association between Aurora B and its activators- Survivin and INCENP, leading to a consequent reduction in Aurora B activity. Additionally, in vitro binding assays demonstrate that, residues 138 to 328 of Xenopus TPX2 (TPX2 B) are sufficient to enhance the interaction between Aurora B and its activator, Survivin. Further, TPX2 B also increases Aurora B kinase activity in an in vitro kinase assay. These data suggest that under endogenous conditions, TPX2 functions as a co-activator of Aurora B by increasing Aurora B-Survivin and Aurora B-INCENP interactions. Importantly, IPs with Panc-1 and CFPAC-1 pancreatic cancer cell lines suggest that this mechanism of Aurora B activation by TPX2 is likely to be conserved in human cancer cell lines. Based upon our results, we conclude that TPX2 enhances Aurora B activity by serving as a scaffold protein for assembly of the CPC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-287. doi:1538-7445.AM2012-LB-287