bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1801: ERK-mediated regulation of NFAT3 enhances CXCR4 expression in HeyA8 ovarian cell line.
Authors: Huang Keven , Kiefer Christine , Kamal Adeela 
Published: August 2014

Abstract
The G-protein coupled chemokine (C-X-C motif) receptor CXCR4 is linked to cancer, HIV, and WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome. While CXCR4 is widely studied and characterized extensively to be over-expressed in multiple human tumor tissues, we have seen poor surface CXCR4 expression in many solid tumor cell lines in vitro. To better understand how CXCR4 is regulated, cells grown under 3-D spheroid conditions were compared to normal adherent culturing conditions. When cultured as 3D spheroids, HeyA8 cells showed a dramatic increase in surface CXCR4 protein levels as well as mRNA transcripts. Furthermore, HeyA8 3D spheroids showed a decrease in pERK levels when compared to adherent cells. Using an inhibitor of the MEK-ERK pathway, the treatment of adherent HeyA8 cells with U0126 resulted in a significant increase in surface CXCR4 expression similar to 3D spheroids. Additional investigation using PCR array showed a wide range of transcription factors being up-regulated but notably a &gt; 20 fold increase in NFAT3 transcription factor. Using a calcineurin inhibitor, cyclosporin A diminished the U0126 treated up-regulation of CXCR4 surface expression. Finally, Chromatin Immunoprecipitation analysis showed direct binding of NFAT3 on the CXCR4 promoter to increase CXCR4 expression in HeyA8 ovarian cell line. Taken together, our results suggest that phospho-ERK levels regulate CXCR4 expression through the NFAT3 signaling pathway.
Citation Format: Keven Huang, Christine Kiefer, Adeela Kamal. ERK-mediated regulation of NFAT3 enhances CXCR4 expression in HeyA8 ovarian cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1801. doi:10.1158/1538-7445.AM2013-1801
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 1803: Transcriptional regulation of nicotinic acetylcholine receptors (nAChRs) by E2F family transcription factors in non-small cell lung cancer.
Authors: Schaal Courtney M. , Pillai Smitha , Johnson Jackie L. , Chellappan Srikumar 
Published: August 2014

Abstract
Nicotine, the addictive component of cigarette smoke, has been shown to promote cell proliferation, migration, invasion, and angiogenesis in multiple cancer types. Earlier studies from our lab had shown that nicotine can promote the growth and metastasis of non-small cell lung carcinoma (NSCLC) in mouse models. While a broad range of nAChRs have been found to be expressed on NSCLC cell lines, nicotine-mediated proliferation, invasion, and migration are facilitated predominantly through the α7 subunit. Consistent with this, α7 nAChR levels are elevated in NSCLC in mice that were administered nicotine. Stimulation of α7 nAChR with nicotine has been reported to activate Src, resulting in inactivation of the retinoblastoma (Rb) tumor suppressor protein and enhancing E2F-mediated transcription. The Rb-E2F transcriptional regulation pathway is known to induce genes involved in cell cycle progression, angiogenesis, and metastasis implicating it in tumor survival and progression. Given this background, attempts were made to elucidate whether nAChR genes are regulated by the Rb-E2F pathway. Analysis of a 2000bp promoter region of the human α7 gene revealed the presence of multiple E2F binding sites. Transient transfection experiments showed α7 to be responsive to multiple E2Fs. E2F1 was found to associate with the α7 promoter via chromatin immunoprecipitation assays. Depletion of E2F genes via small interfering RNA demonstrated a differential regulation of α7 by E2F family members 1-5. These results raise the possibility that exposure to nicotine stimulates the α7 signaling cascade resulting in elevated E2F1-mediated activation of various proliferative promoters, including that of α7 itself in a positive feedback mechanism. In addition to the α7 nAChR, recent genome wide association studies (GWAS) have identified a susceptibility locus for human lung cancer at 15q25.1 which encodes for nAChR subunits α3 and α5. Promoter analysis has revealed that both α3 and α5 have multiple potential E2F binding sites, as well. Preliminary knock down of E2F family members via small interfering RNA has suggested these subunits may also be differentially regulated by the E2F family of transcription factors. Further studies are under way to elucidate the role of E2F in the regulation of nAChR α3 and α5, and how this impacts nicotine signaling as well as growth and progression of NSCLC.
Citation Format: Courtney M. Schaal, Smitha Pillai, Jackie L. Johnson, Srikumar Chellappan. Transcriptional regulation of nicotinic acetylcholine receptors (nAChRs) by E2F family transcription factors in non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1803. doi:10.1158/1538-7445.AM2013-1803
Abstract 1804: Integrative genomics and expression analysis reveals enhanced SENP2-mediated desumoylation and a crosstalk with Neddylation pathway in squamous cell carcinoma of the lung.
Authors: Qian Jun , Wang Jing , Hoeksema Megan D. , Zou Yong , Espinosa Allan V. , Rahman Jamshedur , Zhang Bing , Massion Pierre P. 
Published: August 2014

Abstract
Chromosome 3q26-29 amplification is a critical genomic alteration in squamous cell carcinomas (SCC) of the lung. There remains no consensus on what driver genes may carry this amplicon throughout tumor progression and their functional implications. We hypothesized that the amplification level of a predefined amplicon in a tumor sample can be inferred based on gene expression data. The hypothesis was tested using the TCGA dataset with paired copy number and gene expression data and achieved an accuracy of 90%. Based on the TCGA dataset and six other independent gene expression datasets (GSE4573, GSE8894,GSE2109,GSE3141 and GSE17710), we inferred candidate 3q26-29 drivers by searching for genes that were consistently over-expressed in SCCs with a high-level of 3q26-29 amplification in all seven datasets. The top 20 candidate driver genes includes PSMD2, DCUN1D1,SENP2, ZNF639, FXR1, SENP5,PRKCI, PIK3CA and UBXN7, et al. Using NetWalker we further identified a potential driver network consisting of SENP2, DCUN1D1, UBXN7 and DVL3, which are involved in SUMOlyation and Neddylation pathway. The amplification and overexpression of four genes were confirmed by performing genome-wide Agilent 244k CGH profiling and 44k gene expression profiling on twenty-four SCC tumors. Knocking down using siRNA against SENP2 resulted in greatest cell growth inhibition on 3q26-28 amplified SCC cell line H520. Immunoprecipitation assay showed that SENP2 binds to endogenous MDM2 in H520 cells. Loss of SENP2 leads to increased SUMO1 expression and elevated p53 expression associated with a decrease in MDM2 expression. Furthermore, knocking down SENP2 reduced the expression of DCUN1D1 and DVL3 but not UBXN7 in H520 cells. Together these data suggest that SENP2-mediated desumoylation and crosstalk with the Neddylation pathway contribute to lung SCC progression.
Citation Format: Jun Qian, Jing Wang, Megan D. Hoeksema, Yong Zou, Allan V. Espinosa, Jamshedur Rahman, Bing Zhang, Pierre P. Massion. Integrative genomics and expression analysis reveals enhanced SENP2-mediated desumoylation and a crosstalk with Neddylation pathway in squamous cell carcinoma of the lung. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1804. doi:10.1158/1538-7445.AM2013-1804
Abstract 181: Hepatic retinoid signaling in mouse hepatocarcinogenesis models.
Authors: Shirakami Yohei , Blaner William S. , Shimizu Masahito , Moriwaki Hisataka , Seishima Mitsuru 
Published: August 2014

Abstract
Retinoids are known to possess anti-cancer effects and a clinical trial of a synthetic retinoid for hepatocellular carcinoma (HCC) is ongoing recently in Japan. Hepatic retinoid metabolism is usually impaired during development of liver diseases. Loss of retinoid-containing lipid droplets upon hepatic stellate cell (HSC) activation is one of the first events in the development of liver diseases and retinoid stores are progressively lost from HSCs leading to hepatic fibrosis, cirrhosis, and HCC. In the present study, we employed two types of genetically-modified mice for investigating hepatic retinoid metabolism and signaling in diethylnitrosamine (DEN)-induced mouse hepatocarcinogenesis models. One is lecithin:retinol acyltransferas (LRAT) knockout (KO) mouse which lacks HSC lipid droplets and has much less hepatic retinoid stores, and the other is a transgenic mouse which expresses dominant negative form of retinoic acid receptor (dnRAR) to block retinoid signaling in the liver. Male 15 day-old mice were given intraperitoneal injections of DEN (25 mg/kg body weight). Eight-month-old DEN-treated Lrat KO mice showed lower liver tumor incidence and dnRAR transgenic mice showed higher incidence than that of respective control mice. In the acute phase after DEN injection, dnRAR transgenic mice exhibited higher hepatic levels of inflammatory cytokines. Two days after DEN injection, lower serum levels of alanine aminotransferase and decreased hepatic levels of cyclin D1 were observed in Lrat KO mice. Lrat KO mice also exhibited increased levels of retinoic acid-responsive genes, including p21, lower levels of cytochrome P450 enzymes required for DEN-bioactivation, and higher levels of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). Our results indicate that Lrat KO mice, instead of almost no hepatic retinoid storage, are less susceptible to DEN-induced hepatocarcinogenesis due to increased hepatic retinoid signaling which is accompanied by higher expression of p21 in the liver. In conclusion, retinoid signaling plays a key role in these hepatocarcinogenesis models.
Citation Format: Yohei Shirakami, William S. Blaner, Masahito Shimizu, Hisataka Moriwaki, Mitsuru Seishima. Hepatic retinoid signaling in mouse hepatocarcinogenesis models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 181. doi:10.1158/1538-7445.AM2013-181
Abstract 1815: Genome-wide analysis of the molecular crosstalk between mitogenic and proinflammatory signaling in breast cancer.
Authors: Franco Hector L. , Nagari Anusha , Kraus W. Lee 
Published: August 2014

Abstract
The interplay between mitogenic (e.g., estradiol) and proinflammatory (e.g., TNFα) signaling pathways play key roles in determining the phenotypes and clinical outcomes of breast cancers. Both pathways promote dramatic changes in the transcriptomes of breast cancer cells, as well as downstream cellular effects, but the interplay between these two pathways at the transcriptional level has not yet been analyzed in a comprehensive way across the genome. We have used global nuclear run-on coupled with deep sequencing (GRO-seq), a genomic method that maps the location and orientation of all actively engaged RNA polymerases, to characterize the immediate transcriptional responses of MCF-7 breast cancer cells treated for short durations (40 min.) with either estradiol (E2), TNFα, or both. In addition, we have integrated these data with chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) for both estrogen receptor alpha (ERα), which mediates E2 signaling, and the p65 subunit of the NF-κB transcription factor, which mediates TNFα signaling. Our results indicate extensive transcriptional interplay between these two signaling pathways, which is observed for a number of classical mitogenic and proinflammatory protein-coding genes. In addition, GRO-seq has allowed us to capture the transcriptional crosstalk at genomic locations encoding for long non-coding RNAs (lncRNAs), a poorly characterized class of RNAs which have been shown to play important roles in cancer outcomes. The synergistic and antagonistic interplay between E2 and TNFα also manifests itself at the level of ERα and p65 binding, which relocalize to new binding sites that are not occupied by either treatment alone. Taken together, our results identify rapid, signal-dependent transcriptional changes that occur during proliferative signaling versus inflammatory signaling and show that these effects are more extensive than previously anticipated. Uncovering the transcriptional landscape of these two important pathways outside of the protein coding regions of the genome may lead to new ways of diagnosing and treating breast cancer.
Citation Format: Hector L. Franco, Anusha Nagari, W. Lee Kraus. Genome-wide analysis of the molecular crosstalk between mitogenic and proinflammatory signaling in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1815. doi:10.1158/1538-7445.AM2013-1815
Abstract 1816: SULT1A1 gene expression level is correlated with gene copy number in different human epithelial and breast cancer cell lines.
Authors: Yao-Borengasser Aiwei , Rogers Lora J. , Penny Rosalind B. , Edvana Vineetha K. , Kadlubar Susan A. 
Published: August 2014

Abstract
Sulfotransferase isoform 1A1 (SULT1A1) is a member of a subfamily of cytosolic enzymes which catalyze the transfer of a sulfonate group from 3’-phosphoadenosine 5’ -phosphosulfate (PAPS) to a range of xenobiotic and endogenous compounds such as drugs, carcinogens, and steroid hormones. SULT1A1 plays a role in detoxification of tamoxifen (TAM), a drug for estrogen receptor (ER) positive breast cancer treatment and chemoprevention. Besides its involvement in drug metabolism, SULT1A1 also contributes to increased cancer risk. SULT1A1 activity varies several-fold among individuals. Earlier studies have shown that individuals can possess one to five copies of the SULT1A1 gene. SULT1A1 gene expression is higher in individuals with more than one copy number, although there is no significant difference among individuals who have more than 3 copy numbers. We determined the copy number of SULT1A1 in cell lines ZR75, MCF7, T47D, MDA-MB-231, and MCF10A using a pre-designed Custom Plus TaqMan® Copy Number kit from Life Technology. Similar to the human population, the human cell lines tested also contain one to five copies of SULT1A1. Genomic DNA of MCF7, MDA-MB-231, and MCF10A cells contains only one copy of SULT1A1, while ZR75 DNA contains 3 copies and T47D DNA contains 5 copies of SULT1A1. To determine if copy number correlates with gene expression level, we compared the amount of SULT1A1 mRNA by RT-PCR in each cell line with corresponding copy numbers. Cell lines with one copy of SULT1A1 (MCF7 and MCF10A) had lower gene expression; while cell lines with more than one copy number (ZR75 and T47D) had higher gene expression. ZR75 cells expressed significantly more SULT1A1 mRNA than that of T47D, even though ZR75 DNA has two less copies than T47D cells. Although MDA-MB-231 DNA contains one copy of SULT1A1, no SULT1A1 gene expression was detected, indicating that other mechanisms exist in regulating SULT1A1 gene expression. In summary, the current data suggest that differential SULT1A1 gene expression levels in human breast cancer cells could be partially regulated by its copy numbers. Furthermore, the cell lines tested here could be used as in vitro models to study the mechanisms of SULT1A1 gene expression regulations since the copy number differences in those cell lines represented the copy number differences in human population.
Citation Format: Aiwei Yao-Borengasser, Lora J. Rogers, Rosalind B. Penny, Vineetha K. Edvana, Susan A. Kadlubar. SULT1A1 gene expression level is correlated with gene copy number in different human epithelial and breast cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1816. doi:10.1158/1538-7445.AM2013-1816
Abstract 1819: Over-expression of PIM1 kinase contributes to CYP24A1 gene up-regulation in prostate cancer.
Authors: Luo Wei , Chernov Mikhail , Ma Yingyu , Johnson Candace , Trump Donald 
Published: August 2014

Abstract
The traditional role of vitamin D is in the control of calcium homeostasis and bone mineralization. Over the past 2 decades, studies have demonstrated that vitamin D is useful for the prevention and treatment of various cancers. 24-hydroxylase, encoded by CYP24A1 gene, is the key enzyme which inactivates vitamin D. Increased expression of CYP24A1 has been found in several human tumors. CYP24A1 is regulated directly by 1,25(OH)2D3 (1,25D3) through genomic signaling. Studies have revealed that protein kinase signaling pathways may also be involved in the regulation of CYP24A1 expression. By screening a chemical compound library, we discovered that small chemical compounds with inhibitory activity toward protein kinases including PIM1 and HIPK2 inhibited CYP24A1 expression. Furthermore, siRNA-mediated PIM1 knockdown reduced 1,25D3-induced CYP24A1 mRNA and protein expression in human prostate cancer PC3 cells. In contrast, HIPK2 knockdown had no effect. The serine/threonine kinase PIM1 has been implicated as an oncogene in various human cancers including lymphomas, gastric, colorectal and prostate carcinomas. We analyzed mRNA expression of CYP24A1 and PIM1 in 26 case-matched pairs of human benign and malignant prostate by qRT-PCR. CYP24A1 expression was increased in 6 out of 26 malignant prostate samples compared to benign lesions (&gt; 1.5 fold). PIM1 expression was increased in 10 out of 26 malignant prostate samples compared to benign lesions (&gt; 1.5 fold). Five of the 6 samples with increased CYP24A1 in malignant lesions also had increased PIM1 expression. Fisher's exact test shows that increased CYP24A1 expression is significantly associated with increased PIM1 expression in malignant prostate (P = 0.0184). These data indicate that PIM1 may be involved in increased CYP24A1 expression in prostate cancer.
This study was supported by NIH/NCI grants 5R01CA067267 and 5R01CA095045.
Citation Format: Wei Luo, Mikhail Chernov, Yingyu Ma, Candace Johnson, Donald Trump. Over-expression of PIM1 kinase contributes to CYP24A1 gene up-regulation in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1819. doi:10.1158/1538-7445.AM2013-1819
Abstract 1820: TP63 regulation of epithelial to mesenchymal transition in an experimental prostate cell model.
Authors: Olsen Jan Roger , Øyan Anne Margrete , Rostad Kari , Hellem Margrete R. , Liu Jie , Li Lisha , Micklem David , Haugen Hallvard , Lorens James B. , Ke Xisong , Rotter Varda , Lin Biaoyang , Kalland Karl-Henning 
Published: August 2014

Abstract
Background: p63 is a transcription factor that is central for epithelial homeostasis and development. In our cell culture model of epithelial to mesenchymal transition (EMT) in a human prostate cells, p63 was one of the most down-regulated transcription factors during EMT. This led us to investigate the role of p63 in EMT by a gain and loss of function approach.
Results: Over-expression of the predominant epithelial isoform ΔNp63α in mesenchymal EPT1 and EPT2 cells led to gain of several epithelial characteristics without resulting in a complete mesenchymal to epithelial transition (MET). When p63 was knocked down in epithelial EP156T cells complementary results were observed. Global gene expression analyses found that ΔNp63α induced gene modules involving cell adhesion genes in mesenchymal like cells. ChIP-seq analyses confirmed the enriched binding of p63 to regulatory areas of genes associated with cell adhesion in prostate epithelial cells.
CDH1 and ZEB1 are two elemental factors in the control of EMT. Over-expression and knockdown of these factors, respectively, were not sufficient alone or in combination with ΔNp63α for full reversal of the mesenchymal phenotype in EPT cells.
Conclusion: The partial reversion of epithelial to mesenchymal transition might reflect the ability of ΔNp63α, as a key co-ordinator of several epithelial gene expression modules, to reduce epithelial to mesenchymal plasticity (EMP). The potential of reduced EMP in order to counteract metastasis and the utility of ΔNp63α expression in this regard may provide a novel strategy to counteract the metastatic process.
Citation Format: Jan Roger Olsen, Anne Margrete Øyan, Kari Rostad, Margrete R. Hellem, Jie Liu, Lisha Li, David Micklem, Hallvard Haugen, James B. Lorens, Xisong Ke, Varda Rotter, Biaoyang Lin, Karl-Henning Kalland. TP63 regulation of epithelial to mesenchymal transition in an experimental prostate cell model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1820. doi:10.1158/1538-7445.AM2013-1820
Abstract 1822: An integrated approach to identify clinically relevant long non-coding RNAs (lncRNAs) in cancer.
Authors: Liu X. Shirley 
Published: August 2014

Abstract
Despite growing appreciation of the number and importance of long non-coding RNAs (lncRNAs) in normal physiology and diseases, the knowledge on cancer-related lncRNAs is still limited. We utilized probes from array-based expression profiles that are uniquely mapped to annotated lncRNAs to investigate the expression of 10,207 lncRNAs in about 1,300 tumor samples over four different cancer types. By integrating the expression profiles of these lncRNAs with clinical outcome and somatic copy number alterations (SCNA), we identified lncRNAs that are associated with specific cancer subtypes and clinical prognosis, and predicted those that are potential drivers of cancer progression. We further validated our computational predictions by experimentally confirming the oncogenic functions of two novel lncRNAs in prostate cancer. Our results demonstrate that public genomic data contain a wealth of information on disease-relevant non-coding RNAs, and integrating orthogonal datasets and clinical information could facilitate the discovery of clinically relevant lncRNAs and help prioritize their functional studies.
Citation Format: X. Shirley Liu. An integrated approach to identify clinically relevant long non-coding RNAs (lncRNAs) in cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1822. doi:10.1158/1538-7445.AM2013-1822
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.