bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2326: Understand the telomerase-dependent transcriptional regulation in cancer cells
Authors: Yan TingDong , Liu Chang-Ching , Poon Lai-Fong , Chai Xiaoran , Fullwood Melissa Jane , Ghosh Sujoy , Li Shang 
Published: May 2015

Abstract
We and others have previously demonstrated that modulation of telomerase activity induces rapid and defined changes in genome-wide gene expression profiles in telomerase-positive cancer cells in culture, which point to the possibility of telomerase's involvement in gene regulation. Previous results also indicated the direct involvement of telomerase catalytic subunit-hTERT in transcriptional regulation through its interaction with Brg1 as well as NFkB. Such transcriptional function of hTERT is not dependent on its reverse transcriptase activity, suggesting a novel telomere-independent function of telomerase that promote stem cell proliferation and survival via activation of key genes regulating cell proliferation and survival. To further explore the potential role of hTERT in direct regulation of genome-wide gene expression in cancer cells, we have engineered cancer cells expressing 3xFlag-tagged hTERT from endogenous loci using AAV-mediated recombination. These genetically engineered cells allow the reliable detection and immunopurification of endogenous and functional hTERT in cancer cells. Such unique tools provide the key to identify potential transcriptional targets regulated by hTERT directly in vivo. Using ChIP-seq, we have mapped the genome-wide targets of potential hTERT binding sites in both HeLa S3 cells and HCT116 cells.
Citation Format: TingDong Yan, Chang-Ching Liu, Lai-Fong Poon, Xiaoran Chai, Melissa Jane Fullwood, Sujoy Ghosh, Shang Li. Understand the telomerase-dependent transcriptional regulation in cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2326. doi:10.1158/1538-7445.AM2014-2326
Abstract 2328: COX-2 induce mediated multidrug resistance by activating JNK signal transduction pathway in colorectal cancer
Authors: Li Qi , Sui Hua 
Published: May 2015

Abstract
Chemotherapy is an important therapeutic option for most cancer patients; however, drug resistance causes the failure of chemotherapy and becomes a major obstacle for successful chemotherapy. The overexpression of P-gp has been associated with the resistance to a wide range of anticancer drugs. In the present study, drug-sensitive and multidrug resistant MDR colon carcinoma cell lines were used to examine the role of JNK signaling pathway in P-gp-mediated MDR associated with COX-2. We have found that sp600125, a JNK inhibitor or NS-398, a COX-2 inhibitor, reduced the degree of MDR in MDR cells. This phenomenon was accompanied by a significant decrease in gene level of ABCB1 and protein level of P-gp in MDR cells. In contrast, addition of a JNK inhibitor had no significant effect on the expression of COX-2. Interestingly, inhibition of COX-2 activity led to a decreased level of p-c-Jun at Ser63/73 due to JNK activation. In addition, there is an overexpression of p-c-Jun in MDR cells transfected with recombinant vector pGL3-Basic-COX-2 promoter. Moreover, the intracellular vincristine accumulation significantly increased with treatment of sp600125, or NS-398. In conclusion, our study has provided the first direct evidence that COX-2 induced up-regulation of P-gp in MDR cells, which was associated with an enhanced activity of the c-Jun phosphorylation at Ser63/73. Our findings may facilitate the development of novel antitumor drugs that are more effective against both chemosensitive and MDR cells.
Note: This abstract was not presented at the meeting.
Citation Format: Qi Li, Hua Sui. COX-2 induce mediated multidrug resistance by activating JNK signal transduction pathway in colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2328. doi:10.1158/1538-7445.AM2014-2328
Abstract 2332: Oncogenic mutant KRAS modulates EZH2 expression through MEK-ERK signaling by remodeling gene expression in NSCLC
Authors: Riquelme Erick M. , Shen Li , Wang Jing , Behrens Carmen , Minna John D. , Wistuba Ignacio I. 
Published: May 2015

Abstract
Abstract:
Background. EZH2 overexpression occurs in lung cancer and is associated with a poor outcome. The mechanisms driving EZH2 expression in lung cancer are not fully understood. In this study, we investigated whether pharmacological disruption of signaling MEK-ERK pathway would affect EZH2 expression in a panel of NSCLC cell lines with and without KRAS mutation. Moreover, we analyzed the transcriptome expression following knockdown of EZH2 expression in NSCLC cell lines with different types of KRAS mutations.
Methods. NSCLC cell lines were treated with different doses of MEK inhibitor AZD6244 (0, 0.5 and 1μM) and the expressions of EZH2, MEK and MAPK were determined by Western-blots. Cell lines were transfected with gene-specific EZH2 siRNA and control siRNA. Gene expression profiling was performed using the Illumina Human HT-12 v 4.0 platform. Functional pathway analysis was conducted using the software Ingenuity Pathways Analysis.
Result. We found that pharmacological disruption of signaling MEK-ERK pathways with AZD6244 decreases the expression of MAPK p44/42 and phospho-MAPK p44/42 in all NSCLC cell lines analyzed wild-type and of KRAS mutant status. However, after AZD6244 treatment, EZH2 expression in NSCLC cell lines varied according to the KRAS mutation status: strong reduction only in NSCLC cell lines harboring GtoC mutation, a partial reduction in cells with GtoS and GtoR mutation, and no change in cell lines with GtoD or GtoV mutation and with wild-type KRAS. The gene expression analysis revealed that 3,235 genes were similarly regulated for mutant KRAS GtoC, GtoD and GtoV in NSCLC following EZH2 knockdown compared with KRAS wild-type (P &lt; 0.05). Functional pathways analysis showed that EZH2 knockdown modulated differentially pathways commonly activated in cancer as growth factor signaling, molecular mechanism of cancer and cellular growth, proliferation and development, between cell lines that harbor mutant KRAS GtoC, GtoD or GtoV compared with KRAS wild-type.
Conclusion. Our findings suggest that oncogenic mutant KRAS GtoC, GtoS and GtoR modulate EZH2 expression through MEK-ERK signaling contributing to changes of the expression of genes frequently altered in cancer (Grant support: 5 R01 CA155196 and P50CA70907)
Citation Format: Erick M. Riquelme, Li Shen, Jing Wang, Carmen Behrens, John D. Minna, Ignacio I. Wistuba. Oncogenic mutant KRAS modulates EZH2 expression through MEK-ERK signaling by remodeling gene expression in NSCLC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2332. doi:10.1158/1538-7445.AM2014-2332
Abstract 2333: Nuclear EPS8 as a potential cooperative factor for FOXM1 in cancer cell proliferation
Authors: Ngan Wan-Ling , Yao Kwok-Ming 
Published: May 2015

Abstract
Tumorigenesis arises very often from dysregulated cell proliferation mechanisms. The Forkhead box transcription factor FOXM1 is a critical regulator of cell cycle progression as it affects the expression of genes that control the cell cycle, such as cyclin B1, cdc25B, etc. It is upregulated in various cancers, including cervical cancer. In a yeast two-hybrid screen for partnering factors that interact with FOXM1, we identified Epidermal Growth Factor Receptor (EGFR) Pathway Substrate 8 (EPS8).
The involvement of EPS8 in the EGF signal transduction and actin cytoskeleton organization has been well documented. Despite the lack of an SH2 domain, EPS8 associates with the EGFR and is tyrosine-phosphorylated upon EGF signaling. With its level and phosphorylation strongly induced by serum stimulation, EPS8 is believed to partake in the regulation of cell proliferation. Based on recent observations that EPS8 and FOXM1 expression are both elevated in human cervical cancer cells, and expression levels of EPS8 and FOXM1 are correlated in human head and neck squamous cell carcinoma, we hypothesize that there is crosstalk between these two proteins in vivo to mediate cell cycle progression.
In this study, interaction between FOXM1 and EPS8 was confirmed by co-immunoprecipitation analysis and the domains important for the interaction were defined using yeast two-hybrid assay. The presence of putative nuclear localization and export signals suggests regulation of EPS8 function by nucleocytoplasmic shuttling, consistent with EPS8 being a partnering factor of FOXM1 in the nucleus. Indeed, immunostaining of Hela cells revealed nuclear localization of EPS8 at S and G2/M phases of the cell cycle. Treatment with nuclear export inhibitor leptomycin B led to nuclear retention of EPS8, indicating that EPS8 localization is regulated by Crm-1-dependent nuclear export. Further site-directed mutagenesis defined nuclear export signals on EPS8 which affect the nuclear export/import of EPS8. Moreover, silencing EPS8 using shRNAs in various cell lines led to decreases in FOXM1 and cyclin B expression. Taken together, these data support that EPS8 may function together with FOXM1 in the nucleus and contribute to carcinogenesis via co-regulation of downstream target genes.
Citation Format: Wan-Ling Ngan, Kwok-Ming Yao. Nuclear EPS8 as a potential cooperative factor for FOXM1 in cancer cell proliferation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2333. doi:10.1158/1538-7445.AM2014-2333
Abstract 2334: Identification of differentially expressed genes and somatic mutations in esophageal adenocarinoma cancer patients
Authors: Oster Bodil , Joecker Anika , Hein Anne-Mette K. , Dekker Patrick , O'Neill Robert , Krejci Adam , Arens Anne , Thomson Naomi , Boysen Cecilie , Mønsted Søren , Forsberg Roald , Knudsen Bjarne , Knudsen Thomas , Lussier Richard , Hupp Ted R. 
Published: May 2015

Abstract
High throughput sequencing technologies are currently revolutionizing the cancer research area with rapid improvements in sequencing capacity and time consumption. As a result the most time consuming step has moved from being the sequencing process itself to being the bioinformatic data analysis.
RNA sequencing (RNA-Seq) is used in an increasing number of transcriptomic studies. The great advantage of using RNA-Seq is its ability to precisely quantify transcript levels and identify novel transcripts, isoforms, and splice junctions, while further providing information of the mutational landscape down to single base resolution. To ease the hurdles associated with RNA-Seq data analysis there is an increasing demand for tools that are specifically tailored to RNA-Seq data.
Here we describe how the newly developed CLC Cancer Research Workbench can be used to analyze and visualize RNA-Seq data with ready-to-use workflows that automatically map, quantify, and annotate transcriptomes. We identify differentially expressed genes and transcripts in Illumina HiSeq transcriptomic data from matched tumor and normal samples from four esophageal adenocarinoma cancer patients, and compare the mutational patterns in the samples with the expression values of the corresponding genes.
Results are visualized in a track based genome browser view, which provides the means for quick and easy navigation as well as allowing the user to simultaneously view and annotate multiple samples and different data types (e.g. genes, transcript expression levels, and detected variants).
Citation Format: Bodil Oster, Anika Joecker, Anne-Mette K. Hein, Patrick Dekker, Robert O'Neill, Adam Krejci, Anne Arens, Naomi Thomson, Cecilie Boysen, Søren Mønsted, Roald Forsberg, Bjarne Knudsen, Thomas Knudsen, Richard Lussier, Ted R. Hupp. Identification of differentially expressed genes and somatic mutations in esophageal adenocarinoma cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2334. doi:10.1158/1538-7445.AM2014-2334
Abstract 2338: Functional investigation of the CRD-BP hnRNP-K-Homology domains for C-myc messenger RNA interaction
Authors: Rensburg Gerrit van , Barnes Mark , Lee Chow 
Published: May 2015

Abstract
The coding region determinant binding protein (CRD-BP) is an oncofetal protein, being ubiquitously expressed during embryogenesis, yet highly repressed in adult tissues, except in cancerous tissues [Bell et al, 2013; Mueller-Pillasch et al, 1999]. CRD-BP was inherently identified by its ability to physically associate with c-myc mRNA, and has been shown to protect the transcript from degradation, hence prolonging its mRNA half-life [Prokipcak et al, 1994, Noubissi et al, 2006]. In addition to c-myc mRNA, several other mRNAs bound by CRD-BP have gene products implicated in the development and progression of cancer [Bell et al, 2013]. As an RNA binding protein (RBP), CRD-BP is the Mus musculus variant and homologous to the Homo sapiens IMP-1/Insulin-Like Growth Factor 2 with 99.31% similarity, both categorized into a larger family named VICKZ (Vera/Vg1 RBP, Insulin-Like Growth Factor 1,2,3/IMP-1,2,3, CRD-BP, KOC, and ZBP-1). The VICKZ family of RBPs contains two RNA Recognition Motifs (RRM) and four heterogeneous nuclear ribonucleoprotein [hnRNP]-K-Homology (KH) domains. Deletion analysis had shown that the KH domains, and not the RRM domains, of IMP1 are important for binding RNA substrates. To understand which of the KH domains are critical for interaction with RNA, site-directed mutagenesis was performed to introduce an aspartic acid (D) at the first glycine (G) of the G-X-X-G region in the KH domains of CRD-BP. This D-X-X-G variation was individually introduced to the four KH domains of CRD-BP. These four CRD-BP KH domain variants were expressed, purified and assessed for ability to bind c-myc mRNA using electromobility shift assays (EMSA). In addition, plasmids carrying these variants of FLAG-CRD-BP were transfected into HeLa cells. Immunoprecipitation (IP) using anti-FLAG was performed, followed by RT-qPCR to measure the relative amounts of c-myc mRNA associated with each of the variants as compared to the controls. The in vitro EMSA and IP cell data were all consistent with the notion that all KH domain(s) are critical for CRD-BP-c-myc RNA interaction. Using EMSA, additional binding assessments were carried out in a systematic fashion to determine the smallest region of c-myc mRNA bound by CRD-BP. These results will be presented and discussed, as they provide insight into the role played by the KH domains of CRD-BP in binding RNA, as well as what RNA characteristics are important for binding to CRD-BP.
Citation Format: Gerrit van Rensburg, Mark Barnes, Chow Lee. Functional investigation of the CRD-BP hnRNP-K-Homology domains for C-myc messenger RNA interaction. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2338. doi:10.1158/1538-7445.AM2014-2338
Abstract 2341: CAPG improves breast cancer metastasis through competing with PRMT5 to activate STC-1 transcription
Authors: Huang Sheng , Chi Yayun , Xue Jingyan , Shao Zhimin , Wu Zhaohui , Wu Jiong 
Published: May 2015

Abstract
Recent studies have shown that over-expression of macrophage-capping protein (CapG)improves cancer cell metastasis. Previously, we demonstrated that CAPG was highly expressed in MDA-MB-231 cell line with high metastatic potency compared with its maternal cell line. Sequencing of CapG-cDNA complex showed some overlap with the sequence of a group of DNA-binding proteins, the basic helix-loop-helix family, including the c-myc oncogene. We supposed that CAPG inhibited cancer cell metastasis through modulating gene transcription as a transcription factor.
To examine whether CAPG played a functional role in breast cancer metastasis, three kinds of breast cancer cell lines were applied, including overexpression and knockdown of CAPG. Total RNA from MCF-7 CAPG overexpression cells versus control was obtained. Microarray analysis of global genomic changes was conducted in transcriptional level of these cells. Stanniocalcin 1 (stc-1), an oncogene, was observed significantly up-regulated by over expression of CAPG. Mass spectra and co-immunopreciptation were used to find the potential transcription factors of CAPG.
In breast cancer cell lines, we found that CAPG expression is much higher in relatively aggressive cell line than the mild-nature one on both RNA and protein level. CAPG is also higher in cancer tissues than its adjacent noncancerous tissues (ANCT). Furthermore, it was confirmed that CAPG could directly bind to the promoter of stc-1 to activate stc-1 transcription by luciferase report assay and chip experiments. In CAPG overexpression cell line, knock-down of stc-1 could restrain the CAPG-induced migration and invasion. Interestingly, protein arginine methyltransferase 5 (PRMT5) was found as transcription repressor to compete with CAPG in modulating stc-1 transcription.
In this study, CAPG was approved to play a direct role in participating transcription for the first time. We also supposed that by combining with PRMT5, CAPG could compete with PRMT5, and prevent PRMT5 from repressing stc-1 transcriptional process.
Citation Format: Sheng Huang, Yayun Chi, Jingyan Xue, Zhimin Shao, Zhaohui Wu, Jiong Wu. CAPG improves breast cancer metastasis through competing with PRMT5 to activate STC-1 transcription. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2341. doi:10.1158/1538-7445.AM2014-2341
Abstract 2343: Role of calreticulin in the regulation of MALAT-1 expression in mouse adenocarcinoma cells
Authors: Massaeli Hamid , Viswanathan Divya , Pillai Dhanya , Mesaeli Nasrin 
Published: May 2015

Abstract
Calreticulin (CRT) is a ubiquitously expressed protein, with both calcium binding and chaperone activity. CRT is involved in quality control process during the folding and maturation of proteins in ER. Recently, we showed that overexpression of CRT resulted in the development of metastatic lung adenocarcinoma. In order to examine genes involved in the development of lung cancer we carried out microarray analysis on RNA isolated from mouse lung tumors versus control. In this screen we observed a significant increase in long noncoding RNA (LncRNA) MALAT-1 in the lungs of CRT overexpressing mouse models. MALAT-1 is a LncRNA that has been documented to be upregulated in the human lung adenocarcinoma and associated with metastasis. Our study was to investigate the mechanism of regulation of MALAT-1 expression and role of CRT in this process. We hypothesized that CRT as a regulator of intracellular calcium regulated MALAT-1 expression thus inducing the development of metastatic lung adenocarcinoma in our mice model. Our data showed a significant correlation between intracellular calcium levels and MATAT-1 RNA expression and stability. Treatment of adenocarcinoma cells with BAPTA-AM resulted in a significant reduction in MALAT-1 level. Treating the cells with thapsigargin induced a 2 fold increase in MALAT-1 expression. We also demonstrated that knock down of MALA-1 expression using specific siRNA reduces the proliferation of adenocarcinoma cell. Our data demonstrate for the first time involvement of calcium binding protein CRT and intracellular level of calcium on expression and stability of MALAT-1 involved in development of lung adenocarcinoma.
Funded by NPRP4-043-3-016
Citation Format: Hamid Massaeli, Divya Viswanathan, Dhanya Pillai, Nasrin Mesaeli. Role of calreticulin in the regulation of MALAT-1 expression in mouse adenocarcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2343. doi:10.1158/1538-7445.AM2014-2343
Abstract 2346: The expression of ASPP2 and its new isoform delta-ASPP2 in HCC
Authors: Shi Ying , Liu Kai , Ding Huiguo , Lv Fudong , Lopez Charles , Li Ning , Chen Dexi 
Published: May 2015

Abstract
Purpose: Although full-length ASPP2 is necessary to stimulate p53-dependent apoptosis efficiently, the precise mechanisms and cell contexts that enable this function remain to be clarified. In recent study, we found a new ASPP2 isoform (ΔN-ASPP2) may play an important role in regulating the ASPP2-p53 axis. The present study was undertaken to investigate the expression of isoform of ASPP2 in liver tumor and it would be a domain negative regulation of ASPP2 and would be prognostic significance in HCC.
Experimental Design: 120 HCC tissues and same amount of nonneoplastic liver tissues were analyzed for ASPP2 alone and ASPP2 plus ΔN-ASPP2 mRNA expression by real-time RT-PCR. The ΔN-ASPP2 mRNA was analyzed by RT-PCR and real-time RT-PCR with ΔN-ASPP2 specific forward primers. ASPP2 plus ΔN-ASPP2 P53 downstream effectors of the apoptotic and cell cycle arrest pathway (BAX and P21) were studied in 100 HCC specimens.
Results: The expression of ASPP2 and ΔN-ASPP2 mRNA levels were highly variable in HCC tissues. There was no association between the ASPP2/ ΔN-ASPP2 mRNA level and the p53 status. Expression of full length ASPP2 in pairs were detected in 62 HCC and its adjacent tissue.ASPP2-full mRNA level is significant lower in HCC than that in the tumor surrounding tissue (P=0.0159). Expressions of ΔN-ASPP2 mRNA, ASPP2-total (ASPP2, ΔN-ASPP2 and 53BP2), BAX and P21 in pairs were compared between 72 of HCC and their adjacent tissue. The results showed that ΔN-ASPP2 mRNA (P=0.0435) is significantly higher and ASPP2-total (P=0.0212), BAX (P=0.0057) and P21 (P=0.002) are significantly lower in HCC than that in adjacent tissue. CONCLUSIONS: The high level ΔASPP2 which is in contrast to ASPP2 function and low level ASPP2-full which is a p53 activator in HCC would play an important role in tumor development and tumor senescence.
Citation Format: Ying Shi, Kai Liu, Huiguo Ding, Fudong Lv, Charles Lopez, Ning Li, Dexi Chen. The expression of ASPP2 and its new isoform delta-ASPP2 in HCC. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2346. doi:10.1158/1538-7445.AM2014-2346