bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4063: Estrogen receptor alpha functions as an RNA binding protein to regulate GATA3 protein levels: a novel role for ER
Authors: Joyce Karen , Hostetter Christine , Chamoun George , Keen Judith C. 
Published: February 2011

Abstract
The role of estrogen receptor alpha (ER) as a transcription factor has been well established. ER transcriptionally activates genes by binding to DNA directly within the gene promoter region or by binding to DNA indirectly through protein-protein dependent mechanisms. Many ER-responsive genes that are activated through ER-mediated transcriptional activation have been identified, including GATA3. While the role of GATA3 in breast cancer still remains largely unknown, numerous reports have shown that ER and GATA3 are coordinately expressed in breast cancer and that ER may play a role in regulating GATA3 expression. A recent report by Eeckhoute et al (2007) has shown that ER transcriptionally activated GATA3 expression in T47D breast cancer cells. Using MCF7 cells, we have recently identified a novel role for ER as an RNA binding protein that binds to GATA3 mRNA. Interestingly, silencing of ER using siRNA probes slightly increased GATA3 mRNA levels, however GATA3 protein levels decreased significantly. This decrease in protein was not due to improper export of GATA3 mRNA from the nucleus to the cytoplasm where protein translation occurs, as GATA3 mRNA expression was equivalent in both the nuclear and cytoplasmic compartments. This suggested that the decrease in protein expression was not due to impaired GATA3 mRNA transport but could be due to impaired protein translation. Since silencing of ER had dramatically different effects on RNA and protein levels, this data suggested that ER protein may function as an RNA binding protein that binds to the GATA3 mRNA to regulate its protein translation. Using biotin pulldown techniques, we found that ER does function as an RNA binding protein by binding directly to a site within a 125 nucleotide region of the GATA3 3‘UTR. This role of ER as an RNA binding protein is consistent with the data of Lanz et al (1999, 2000) that demonstrated that ER protein can bind to an RNA transcript, the steroid receptor co-activator, SRA. When bound to SRA, however, ER did not alter the RNA levels or protein expression of SRA but did result in increased activation of ER. Therefore, our data is the first to identify a novel role for ER as a RNA binding protein that can regulate the protein expression of the RNA transcript to which it is bound. Altering such ER-RNA interactions could potentially provide a new therapeutic avenue for the treatment of breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4063.
Abstract 4069: The p47 Phox mediated redox-signal promotes myogenesis via p38 MAPK regulated microRNA-206
Authors: Song Junkyu , Choi Young Eun , Kim Hye Ok , Cho Chang Hoon , Yoon Kyung-Sik ,   Department of Biochemistry and Molecular Biology(BK21 project), MRC for Bioreaction to ROS and B
Published: February 2011

Abstract
miR-206 is reported that one of the skeletal muscle specific myogenic factors which are halt the cell cycle via inhibition of DNA polymerase-alpha. So far, MyoD and AP1 are as well as known for miR-206 transcription factors. In this study, we take the evidence of another transcription factor MEF-2 which have a capacity for miR-206 expression in myogenesis. In addition, a novel miR-206 transcription factor is belonging to p38 MAPK activities that can be regulated by p47 Phox mediated redox-signal. It is hypothesis for a novel role of myogenic miR-206 regulation that p47 Phox generated redox-signal contributes to skeletal muscle differentiation via p38 MAPK activated miR-206. Followed the hypothesis, we were analysis the miR-206 promoter region (&gt;-2k) by MatInspector (Promotor analysis tool, www.genomatix.de) for found out another plausible transcription factors and compare the miR-206 expression levels in SB203580 (p38 MAPK inhibitor), DPI (p47 Phox inhibitor) treated and differentiation condition by real-time PCR. Then, measuring the differentiation induced ROS during myogenesis by FACS. Moreover, we analyzed the expressions of myogenic factors and cell cycle involved molecules, including DNA polymerase-alpha, with immunoblotting. As a result, we hunt out a specious myogenic transcription factor MEF-2 that was not reported as a miR-206 expression factor. Both MEF-2 upstream activator p38 MAPK and p38 MAPK stimulating redox generator p47 Phox inhibition were accompanied with miR-206 down regulation. Besides, hindering of p38 MAPK and p47 Phox observed restoration of DNA polymerase-alpha transcription/translation levels in myogenic condition. Accordingly, we suggest that ROS activated p38 MAPK down-stream transcription factor MEF-2 may showed to a novel regulation factor of miR-206 in mouse skeletal muscle myogenesis.
Key words: microRNA-206(miR-206), p47 Phox, p38 MAPK, MEF-2
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4069.
Abstract 4077: Knockdown of the aryl hydrocarbon receptor altered tumorigenic properties of human breast carcinoma cell lines
Authors: Goode Gennifer D. , Eltom Sakina E. 
Published: February 2011

Abstract
Previous studies have found that AhR is overexpressed and constitutively activated in several breast carcinoma cell lines and the expression levels showed strong correlation with the degree of the tumor malignancy. The objective of this study is to examine the effect of reducing the expression levels of AhR in metastatic human breast carcinoma (HBC) cell lines on their tumorigenic properties; specifically cellular growth, invasion into matrigel, and migration. We designed a series of short hairpin RNA (shRNA) targeting AhR and cloned them in pSuper retroviral vectors, and viruses expressing shRNA were used to infect a battery of HBC cell lines including MDA-MB231, MDA-MB468, BT549 and MT2 to generate cell lines that permanently express siRNA targeting AhR. Clonal cell lines with 50%-90% knockdown of AhR were isolated and characterized in vitro for their tumorigenic properties in comparison to the scramble RNA-expressing control cell lines. Cell cycle analysis by fluorescence-activated cell sorting showed that knock down of AhR expression decreases transition of cells from G1 to S and their progression to G2/M phases of cell cycle. This was seen as an increase of cells in G0/G1 (49% to 61%) and a decreased number of cells in S (26% to 21%) and G2/M phases (25% to 17%). This effect was coupled with a prolonged doubling time and a decreased cellular proliferation. Cells with AhR knock-down exhibited a decreased anchorage independent growth; forming less numbers of colonies in soft agar than control cells. Modified Boyden Chamber invasion assay coupled with fluorescence detection demonstrated that clones of HBC with AhR knock down levels exhibited substantially reduced invasiveness and diminished potential to invade matrigel. These clonal cell lines further exhibited reduced ability to migrate, as measured by scratch wound test. These observations collectively demonstrate a major role for the AhR in regulating tumorigenic phenotypes of metastatic breast cancer. Currently breast cancer prevention research focuses on the identification of novel approaches and/or novel targets. Our findings may establish the potential of targeting AhR as one of the prevention strategies for breast cancer.
Supported by RR03032 15, CA91408-01 and DAMD17-02-01-0483 grants.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4077.
Abstract 4080: Global changes in gene expression during phorbol ester-induced differentiation of human acute myeloid leukemia cells
Authors: Swain Emily , Solaiman Adnan , Ratnayake Senaka , Larson Abby , Deeds Ryan , Conner Amy , Forrester Jeffrey , Roberts Michael 
Published: February 2011

Abstract
This study seeks to elucidate the molecular mechanisms by which the acute myeloid leukemia cell line, HL-60, is induced to differentiate into macrophage-like cells following exposure to phorbol 12-myristate 13-acetate (PMA). Changes in gene expression over the time course of PMA treatment were measured by DNA microarray analysis and select genes shown to be significantly up- and down-regulated were validated by quantitative, real-time PCR. Functional studies of transcription factor binding activities were performed by the electrophoretic mobility shift assay (EMSA). Novel findings include the rapid and sustained induction of mRNA levels for a group of CC chemokine genes (CCL2, CCL3, CCL3L1, CCL4, CCL4L1 and CCL4L2). These genes displayed 10 to 50-fold expression level increases that were observed within 3 hours of treatment and were maintained through 6 hours post-induction. The anti-proliferative effects of these peptides are being examined on a variety of leukemia cell lines. Among the most highly induced early genes were others known to encode inflammatory response proteins (TNF, IL8, C3AR1). In addition, the transcription factor profile is dramatically altered early in the differentiation time course, with the predicted activation of AP-1 family members (JUNB, FOSL1) and the concomitant inhibition of NFKB (TNFAIP3, NFKBIA, NFKBID). Other transcription factor genes were transiently up regulated (MAFB, GATA2, ETS2) and c-MYC expression was significantly down regulated and remained low during the differentiation course. Pathway analysis was used to predict gene expression changes occurring later in the differentiation process and was tested by microarray analysis. Early events in the genetic re-programming of HL-60 cells in response to the differentiation inducer PMA includes a massive up-regulation of chemokine genes and alteration of the transcription factor profile. The implication of these gene expression changes will be discussed in the context of differentiation therapies for acute myeloid leukemia.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4080.
Abstract 4088: Effects of exposure to particulate matter on methylation of miRNA genes coding for miR-21 and miR-222
Authors: Motta Valeria , Bollati Valentina , Marinelli Barbara , Hou Lifang , Apostoli Pietro , Bonzini Matteo , Nordio Francesco , Pegoraro Valeria , Tarantini Letizia , Schwartz Joel , Bertazzi Pieralberto , Baccarelli Andrea 
Published: February 2011

Abstract
BACKGROUND: Inhalation of Particulate Matter (PM) and PM metal components has been associated with increased risk of lung cancer. MicroRNAs (miRNAs) are small, non-coding RNAs with an important role in biological activities and are linked to human diseases such as cancer.
miRNA expression needs tight regulation, which also takes place at the epigenetic level. miRNAs undergo regulation by DNA methylation in miRNA coding genes, associate with silencing of miRNA expression. Increased expression of miR-21 has been implicated in various processes involved in carcinogenesis, including inhibition of apoptosis, promotion of cell proliferation and stimulation of tumor growth by targeting multiple tumor/metastasis suppressor genes. In cancer cells miR-222 promotes cell proliferation by targetting the cell cycle inhibitor and tumor suppressor p27.
AIMS: We evaluated the effects of exposure to PM and PM metal components on candidate miRNAs methylation (miR-222 and miR-21) in 63 workers of an electric-furnace steel plant with well-characterized exposure.
METHODS: We measured miR-222 and miR-21 methylation in blood leukocyte RNA obtained from 63 workers on the first day of a workweek (baseline) and after three days of work (post-exposure). Quantitative miRNA methylation analysis was performed through bisulfite PCR Pyrosequencing. We estimated individual exposures to PM1, PM10, coarse particles and PM metal components (chromium, lead, cadmium, arsenic, nickel, manganese) between the baseline and post-exposure measurements.
RESULTS: miR-222 and miR-21 methylation was significantly decreased in post-exposure samples, compared with baseline (post-exposure=60.07±9.38, baseline=63.05±6.38; p=0.013 for miR-222; post-exposure=62.47±6.87, baseline=66.24±6.32; p=0.004 for miR-21). In post-exposure samples, miR-222 methylation was negatively associated with the average exposure to the levels of PM (βstd=-0.012, p=0.03 for PM10, βstd=-0.579, p=0.005 for PM1 and βstd=-0.013, p=0.032 for Coarse) and to the levels of PM metal components (βstd=-111.345, p=0.008 for Chromium and βstd=17.195, p=0.023 for Arsenic).
CONCLUSIONS: Changes in miRNA methylation may represent a novel epigenetic mechanism mediating responses to PM and its metal components. Whether these modifications have a role in the initiation and progression of cancer needs to be evaluated in future studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4088.
Abstract 4096: Diffused intrinsic pontine glioma: An analysis of coding and non-coding RNA species
Authors: Sandza Annie , MacDonald Tobey J. , Hill D. Ashley , Nazarian Javad 
Published: February 2011

Abstract
Diffused intrinsic pontine glioma (DIPG) is one of the most difficult pediatric cancers to treat. To date, there is only scant information on the molecular characteristics of this tumor because of the paucity of adequate tissue for investigation due to its inoperable location within the brainstem. In an attempt to uncover the pathogenesis of DIPG, we have generated comprehensive molecular profiles of coding and non-coding RNA species obtained from pediatric DIPG autopsy specimens. Coding and non-coding RNA species play an important role in oncogenesis. Micro RNAs (miRNAs or miRs) are the more recent non-coding RNA species that have been shown to play an essential role in cancer development and cancer biology. Our aim was to gain insight into the molecular underpinnings of DIPG by generating the complete miRNA and mRNA profiles of the tumor.
Three frozen autopsy DIPG specimens were analyzed. Adjacent non-tumor areas were identified by a neuropathologist and used as controls. Total RNA was extracted and coding and non-coding small RNA were profiled using the Affymetrix platform. Human and viral non coding RNAs (n=13) were shown to be differentially expressed in DIPG tumors compared to the adjacent normal tissues. RNA species that showed to be dysregulated were further validated by RT-PCR (ABI platform). Furthermore, correlation analyses were done to assess expression levels of mRNAs and their corresponding miRs. Our preliminary data indicates specific dysregulation of micro RNA and RNA species that control cellular proliferation and tumorigenesis.
Although preliminary, this is to our best knowledge, the first report of comprehensive RNA profiling of DIPG. Correlation of coding and non-coding RNA species observed here will require further validation. Understanding the molecular makeup of DIPG will provide insight into its pathogenesis and perhaps lead to the development of targeted therapeutics for this disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4096.
Abstract 4098: The HMGA1-COX-2 axis: A molecular pathway leading to tumor progression in human pancreatic adenocarcinoma
Authors: Hillion Joelle , Cello Francescopaolo Di , Smail Shamyra , Griffin Matthew , Cope Leslie , Maitra Anirban , Huso David , Resar Linda 
Published: February 2011

Abstract
Pancreatic ductal adenocarcinoma is a highly lethal cancer accounting for over 160,000 deaths worldwide each year. Despite the high prevalence of pancreatic cancer, the molecular events that lead to tumor progression are poorly understood. The high-mobility group A1 gene (HMGA1) is enriched in diverse, high-grade cancers and embryonic stem cells. This gene encodes the HMGA1a and HMGA1b chromatin remodeling proteins, which function in regulating gene expression. We previously showed that HMGA1 induces oncogenic transformation in cultured cells and causes aggressive cancers in transgenic mice. Moreover, we found that high HMGA1 protein levels correlate with poor differentiation status and decreased survival in a study of &gt; 100 primary pancreatic ductal adenocarcinomas. These findings suggest that HMGA1 could drive a poorly differentiated, stem cell-like state and tumor progression in pancreatic ductal adenocarcinoma. In cultured, human pancreatic cells that overexpress K-RAS (HPNE-K-RAS cells), forced overexpression of HMGA1a leads to increased migration, invasion, and a transformed phenotype with anchorage-independent cell growth in soft agar. Because cyclooxygenase-2 (COX-2) is a downstream gene directly activated by HMGA1a in uterine cancers, we investigated the role of the HMGA1-COX-2 pathway in pancreatic adenocarcinoma. Our preliminary data suggest that HMGA1a and COX-2 mRNA levels are positively correlated in a pancreatic cancer cell lines. By chromatin immunoprecipitation, we found that HMGA1a binds to the COX-2 promoter in human pancreatic adenocarcinoma cells. Moreover, COX-2 inhibitors block tumorigenesis in human pancreatic cancer xenografts in nude mice. Taken together, our studies suggest that HMGA1a promotes tumor progression through up-regulation of COX-2 and this pathway could be targeted to treat or prevent human pancreatic adenocarcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4098.
Abstract 411: Pathway analysis of gene-lists associated with platinum-based chemotherapy resistance in ovarian cancer: the big picture.
Authors: Helleman Jozien , Smid Marcel , Jansen Maurice , van der Burg Maria , Berns Els 
Published: February 2011

Abstract
Objective. Ovarian cancer is the leading cause of death from gynecological cancers in the Western world [1]. The overall 5-year survival is only 30% [2], which is for a significant part due to platinum-based chemotherapy resistance. In this study, we performed a pathway analysis on nine published gene-sets associated with platinum resistance in ovarian cancer, including a study by us. With this exploratory study, we aim to identify overlapping pathways associated with platinum-based chemotherapy resistance mechanisms in ovarian cancer.
Methods A Gene Ontology (GO) analysis and Ingenuity Pathway Analysis (IPA) was performed to determine which functional processes were differentially represented in the combined gene-lists of nine studies (457 genes) compared to all Unigene identifiers or the Ingenuity knowledge base.
Results. The GO and IPA analysis resulted in the generation of 23 gene networks, and showed that 13 GO processes (&gt;=2 times enriched), 71 canonical pathways (p&lt;0.05,), eight toxicity pathways (p&lt;.05) and 74 biological functions (p&lt;0.005) are significantly associated with the 9-study gene set.
Conclusion and recommendations. Several pathways identified have previously been shown to be associated with therapy resistance: these include ‘oxidative stress response mediated by Nrf2’, ‘TP53 signaling’ and ‘TGFbeta signaling’. The role of TGFbeta signalling as well as related miRNAs identified in the network analysis in epithelial-to-mesenchymal transition (EMT) and stemness as well as the possible relation with platin-based chemotherapy resistance is further discussed in detail.
We propose that future international cooperation should aim at a uniform pooled-analysis of the wealth of ovarian cancer array data already available. This will enhance the power of each separate ovarian cancer study and can lead to promising results.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 411.
Abstract 4115: Pituitary adenylate cyclase activating polypeptide causes the transactivation of epidermal growth factor receptors in lung cancer cells
Authors: Moody Terry W. , Mantey Samuel A. , Jensen Robert T. 
Published: February 2011

Abstract
Pituitary adenylate cyclase activating polypeptide (PACAP) is an autocrine growth factor for some lung cancer cells. The activated PAC1 receptor (R) causes phosphatidylinositol turnover, elevates cyclic AMP and increases proliferation of lung cancer cells (Zia et al., Cancer Res. 55:4886 (1995)). PAC1R mRNA is present in NSCLC cell line NCI-H838, which has epidermal growth factor (EGF)R. PACAP or EGF stimulated the proliferation of NCI-H838 cells whereas PACAP(6-38) or gefitinib inhibited growth. To investigate the cellular basis of these actions, the ability of PACAP to alter EGFR function was investigated using NSCLC cells. PACAP, but not the closely related vasoactive intestinal peptide (VIP) significantly increased EGFR tyrosine phosphorylation (4-fold) 2 min after addition to NCI-H838 cells. The ability of PACAP to increase EGFR or ERK tyrosine phosphorylation was inhibited by PACAP(6-38) (PAC1R antagonist), gefitinib (EGFR tyrosine kinase inhibitor), PP2 (Src inhibitor), GM6001 (matrix metalloprotease inhibitor), or antibody to transforming growth factor (TGF) α. These results suggest that PACAP may increase the rate of release of TGFα from NCI-H838 cells, resulting in elevated EGFR tyrosine phosphorylation. PACAP stimulation of EGFR tyrosine phosphorylation was inhibited by addition of N-acetylcysteine (anti-oxidant), tiron (superoxide scavenger), DPI (NADPH oxidase inhibitor) or U-73122 (Phospholipase C inhibitor) but not H89 (protein kinase A inhibitor) to NCI-H838 cells. These results indicate that PACAP, a growth factor for NSCLC, causes transactivation of the EGFR in an oxygen-dependent manner that involves phospholipase C but not protein kinase A.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4115.