bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1249: Modulation of epidermal growth factor induction of migration by integrin-linked kinase
Authors: Dagnino Lina , Ho Ernest 
Published: August 2012

Abstract
Epidermal growth factor (EGF) signaling is central for proliferation, survival and motility in epithelial cells. Cell migration is an obligatory prerequisite for metastasis and requires the development of front-rear polarity. EGF stimulation in various epithelial cell types induces formation of protrusions and migration via RhoG and Rac1 activation. We now demonstrate that treatment of primary epidermal keratinocytes with EGF, but not with other growth factors that promote cell migration, induces cell polarization mediated by complexes containing RhoG, integrin-linked kinase (ILK) and “Engulfment and Cell Motility-2” (ELMO2). This process requires the tyrosine kinase activity of the EGF receptor. Further, ELMO2, ILK, Rac1 and integrin beta1 are obligatory effectors in this pathway, as inactivation or knockdown of the genes or mRNA encoding these proteins abrogates the stimulatory effect of EGF. Thus, we have identified a novel pathway that links EGF receptor stimulation with RhoG/ELMO2/ILK complexes and activation of Rac1 in the acquisition of front-rear polarity.
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 1249. doi:1538-7445.AM2012-1249
Abstract 1251: A role for lactate dehydrogenase in the c-Met/HGF signaling axis
Authors: Gray Alana L. , Minutolo Filippo , Cardelli James A. 
Published: August 2012

Abstract
Tumor cells often display a glycolytic phenotype, even in the presence of oxygen; a phenomenon known as the Warburg effect. The ability of cancerous cells to perform aerobic glycolysis is unique when compared to non-cancerous cells, and therefore, presents a possible therapeutic target for elimination of cancer cells that rely on aerobic glycolysis. Activation of the receptor tyrosine kinase, c-Met, by hepatocyte growth factor (HGF) is a major contributing event in the progression of prostate cancer (PCa). Signaling through this receptor leads to increased cell motility, proliferation, invasion and metastasis. Studies have shown that targeting this signaling axis can greatly reduce the number of bone metastases that arise from primary PCa tumors. Oxamate, a lactate dehydrogenase (LDH) inhibitor, and 2-deoxyglucose (2-DG) are known glycolytic inhibitors. Our studies have found that oxamate reduced c-Met activation and HGF-induced cell motility, while 2-DG had no effect. In order to confirm that oxamate was targeting LDH-A or LDH-B, we created LDH-A, LDH-B, and LDH-A/B knockdown (KD) DU145 cells. Although all of the clones used in the experiments had greater than 70% KD, we were unable to recapitulate the effects seen with oxamate. We believe that this could be due to incomplete KD. In support of this, use of a specific LDH-A (πFly-21) inhibitor significantly reduced c-Met activation and HGF-induced cell motility. Together, these data support a role for LDH-A in facilitating HGF-induced c-Met activation. Because oxamate is a direct LDH inhibitor, we hypothesized that oxamate would have a greater reduction in lactate (LA) export from cells than 2-DG; however, both, oxamate and 2-DG reduced LA production by approximately 75% in DU145 prostate cancer cells. Therefore, the ability of oxamate to reduce c-Met activation is not apparently due to a decrease in LA export. However, it is possible that LA import via monocarboxylate transporter 1 (MCT1) activity may be important for c-Met activation and downstream signaling events. In support of this, KD of MCT1 resulted in reduced c-Met activation and blocked HGF-induced cell motility. These data indicate a potential connection between LDH activity/lactate import and the c-Met signaling axis, suggesting that inhibition of these processes may be a new mechanism for preventing c-Met driven metastatic events.
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 1251. doi:1538-7445.AM2012-1251
Abstract 1258: High-density protein lysate arrays: an essential tool in assessing antibody specificity for clinical applications
Authors: Baruch Dror I. , Ma Donghui , Shu Youmin , Sun Zairen , He Wei-Wu 
Published: August 2012

Abstract
Antibodies for clinical applications require rigorous scrutiny qualifying them for diagnostics or therapeutic use. However, this is a lengthily and complicated process that provides only limited conformation. Protein microarrays are new tools that can determine the specificity and reactivity of Abs and help identifying their target in less than a day. We created a high-density protein array comprised from more than 10,000 over-expressed protein lysates made in human HEK293T cells. We tested more than 15 available antibodies to two cancer targets; the excision repair cross-complementation group 1 (ERCC1) and the receptor tyrosine kinase ERBB2 (Her2/neo). Our results demonstrated the ability of the lysate array in determining the specificity of antibodies with a single fast and easy assay. ERCC1 is a predictor of resistance to platinum based drugs and for poor prognosis in cancer. The commonly used anti ERCC1 antibody, mAb 8F1, is known to give non-specific cytoplasmic staining and to cross-react with an unknown protein of similar size. We tested 10 commercially available Abs to ERCC1 and identified four mono-specific ones (TrueMAb OriGene). Most of these specific Abs gave higher reactivity than clone 8F1. With this test we also identified a cytoplasmic protein of appropriate molecular weight that is cross-reacting with mAb 8F1. The above results were corroborated by WB analysis and IHC assays supporting the validity of this type of assays. We extended our tests to include anti ERBB2 Abs as this important biomarker is indicative for the use and response to the drug Herceptin. Our tests included mono and poly clonal antibodies and clone 4B5, a rabbit mAb currently used for IHC diagnostic. We found clone 4B5 to be reactive with two additional proteins besides ERBB2, one of them is ERBB4. We also tested a rabbit polyclonal anti ERBB2 serum and found it to be reactive with additional proteins unrelated to those recognized by mAb 4B5. Three out of the four mouse mAbs tested (TrueMAb OriGene) were determined to be specific. We submit that the over-expression protein lysate arrays can establish the reactivity and specificity of Abs and identify unknown targets. The speed and convenience of these assays make them an important tool in developing Abs for clinical use.
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 1258. doi:1538-7445.AM2012-1258
Abstract 1261: A mesodissection system for accurate, rapid, and economical recovery of tissue from slide mounted tissue sections
Authors: Adey Nils B. , Parry Robert J. , Birch Lilia , Paxton Christian N. , Ghaffari Siavash , Herrmann Mark G. , Geiersbach Katherine B. 
Published: August 2012

Abstract
We have developed a prototype system for slide mounted tissue dissection capable of resolution between manual methods (i.e. scraping tissue off of microscope slides) and laser capture microdissection (LCM); here we test the performance of this system. The mesodissection instrument employs a specialized milling tip that simultaneously dispenses and aspirates liquid in order to capture tissue fragments displaced from the slide surface. The accompanying software is capable of transferring electronically indicated target regions between neighboring tissue sections to guide the dissection process. Resolution and accuracy of the system were accessed by microscopic inspection of the dissected region; resolution is the smallest recoverable area and accuracy is the difference between the actual dissected region and the desired region. Purity is defined as the percentage of desired tissue retrieved from a FFPE tissue block made from a human tumor xenografted into mouse, and accessed using real-time PCR amplification of species-specific repetitive DNA elements, as well as unique genomic regions. Efficiency is defined as total DNA recovered relative to manual methods, as quantified by PicoGreen fluorescence. Currently, the system is capable of 0.3 mm resolution and accuracy better than 0.1 mm compared to a desired boundary. Purity is greater than 90% at 0.1mm from the mouse-human tissue boundary. Efficiency is comparable to manual methods when virtually all tissue is recovered from the region of interest. Improvements to the current prototype are ongoing with the goal of less than 0.1 mm resolution. The mesodissection system provides an inexpensive alternative to the limited resolution of manual dissection methods and the high cost and low recovery efficiency of LCM. Digitally targeted dissection using tissue sections derived from adjacent portions of a tissue block allow for determination of a region of interest from a slide optimized for visualization and recovery from a slide optimized for dissection.
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 1261. doi:1538-7445.AM2012-1261
Abstract 1281: MALDI imaging mass spectrometry of three-dimensional cell culture systems
Authors: Hummon Amanda B. , Li Haohang , Weaver Eric 
Published: August 2012

Abstract
3D cell cultures have increased complexity compared to simple monolayer and suspension cultures, recapitulating the cellular architecture in the body. For example, many colon cancer cell lines form rounded heterogeneous spheroid structures that mimic the pathophysiological properties of tumors when grown under appropriate cell culture conditions. Classical imaging methodologies, like immunohistochemistry, are commonly used to examine the distribution of specific species within the spheroids. However, there is a need for an unbiased discovery-based methodology that would allow examination of protein/peptide distributions in 3D culture systems, without a need for prior knowledge of the analytes. We have developed MALDI imaging mass spectrometry protocols to examine protein distributions in 3D cultures models. Using the HCT 116 colon carcinoma cell line, we have grown spheroids measuring 1 mm in diameter for MALDI IMS imaging. We detect changes in the spatial distribution of proteins across the spheroids by IMS. While most proteins are distributed across the structures, some are localized to either the proliferative outer rim of the spheroids or to the central necrotic core. We are now expanding our studies to map the changes in protein distribution that accompany knockdown of E-cadherin (CDH1). We are inserting inducible shRNAs targeting CDH1 into HCT 116 cells. Once our cells stably express the shRNAs, we will grow spheroids and then trigger knockdown of CDH1 expression. We will map changes in protein expression over a time course using the MALDI imaging mass spectrometry protocols we have developed. As CDH1 is a critical component of cell-cell junctions, we anticipate that its reduction will trigger phenotypic changes in the spheroid structures. In addition, we expect to see a shift in transcriptional activity that correlates with activation of the Epithelial-Mesenchymal Transition. Our unbiased protein mapping technology enables us to examine previously observed protein changes that result from CDH1 reduction.
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 1281. doi:1538-7445.AM2012-1281
Abstract 1282: NCI's Clinical Proteomic Tumor Analysis Consortium
Authors: Rivers Robert C. , Mesri Mehdi , Kinsinger Chris , Boja Emily , Hiltke Tara , Rodriguez Henry 
Published: August 2012

Abstract
Mission: The Clinical Proteomic Tumor Analysis Consortium (CPTAC) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of robust, quantitative, proteomic technologies and workflows. Goals: The overarching goal of CPTAC is to improve our ability to diagnose, treat and prevent cancer. To achieve this goal in a scientifically rigorous manner, the National Cancer Institute (NCI) launched CPTAC to systematically identify proteins that derive from alterations in cancer genomes and related biological processes, and provide this data with accompanying assays and protocols to the public. Genomics initiatives such as The Cancer Genome Atlas (TCGA) have characterized and sequenced the genomic alterations from several types of cancer. CPTAC will leverage its analytical outputs by producing a unique continuum that defines the proteins translated from cancer genomes in order to link genotype to proteotype and ultimately to phenotype. Scientific Approach: The structure of CPTAC is designed to facilitate the efficient implementation of a two-step developmental pipeline, Discovery and Verification. The pipeline originates with the CPTAC Resource Center, which will provide a set of high-quality, genomically characterized clinical biospecimens from patients with a single type of cancer. The Discovery Unit of each Proteome Characterization Center (PCC) will use a set of proteomic technologies to comprehensively analyze the protein composition of this set of biospecimens including mapping proteome to genome and detecting and quantifying protein products that correspond to genomic aberrations. All data from the Discovery Units will be shared within the network via the CPTAC Data Center. Based on this aggregate data set, each Discovery Unit will select and prioritize cancer-related proteins for potential use in the verification step. The selected lists of prioritized proteins by the Discovery Units will be consolidated and collectively prioritized. The Verification Unit of each PCC will develop targeted assays against corresponding protein targets as assigned by the verification plan. The Verification Units will then verify the biomarker candidates by performing these assays in clinically relevant cancer biospecimens (provided by the CPTAC Resource Center). Data from these verification studies will be shared via the CPTAC Data Center. These verified proteins will serve as high-value targets to other initiatives involved in clinical qualification studies.
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 1282. doi:1538-7445.AM2012-1282
Abstract 1283: A study towards identification of plausible protein markers of squamous cell carcinoma
Authors: Mahajan Manish , Manral Pallavi , Saraswat Mayank , Shukla N K. , Srinivasan A , Yadav Savita 
Published: August 2012

Abstract
Oral cancer is a group of carcinoma that accounts for most common cancer related morbidity in India and 6th most common in western world. Use of Clinical proteomics is a novel way of studying differential proteins in diseased and non- diseased states. 2 - Dimensional Gel Electrophoresis followed by mass spectrometry was used to study the differential protein expression in case of squamous cell carcinoma of buccal pouch using human whole saliva as sample. It was found that there was consistent over - expression of three proteins viz., Cytokeratin type I, Cytoskeletal Associated Protein −2 and a hypothetical protein. Elevation of cytokeratin expression is a well-known tool for immunohistological staining for various cancers of epithelial origin. Cytoskeletal Associated Protein −2 is p53 target genes whose functions are still under scrutiny but related to microtubule stabilization during mitosis. This may be implicated in causing aneuploidy in cancer cell, thus, affecting their overall prognosis. This finding in other cases may be used as a method to segregate cases of buccal pouch cancer as poor prognosis and hence, early intervention and better treatment outcome. Over expression of hypothetical protein in our results still needs further experimentation to vindicate our findings.
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 1283. doi:1538-7445.AM2012-1283
Abstract 1285: A functional liaison between E2F and aberrant ETS oncogenes
Authors: Bilke Sven , Schwentner Raphaela , Fan Yang , Kauer Max , Walker Robert L. , Kovar Heinrich , Melyzer Paul S. 
Published: August 2012

Abstract
Timing, mode and amplitude of gene regulation depend on the tissue specific dynamic composition of transcription factor complexes. Abnormalities of the constituents of the complex are expected to modify the regulatory behavior of the entire module. Here we report a novel E2F-ETS proliferation control module in Ewing's sarcoma. FLI1 and other ETS factors are frequently found to be fused to EWS in this highly aggressive pediatric cancer of the bone. In a genome-wide localization analysis of EWS/FLI1 as well as E2F3 by ChipSeq, two patterns associated with distinct gene sets and modes of regulation were identified and integrated with gene expression data. EWS/FLI1 significantly colocalized with E2F3 to proximal promoters of activated proliferation genes while EWS/FLI1 binding independent of E2F3 occurred predominantly distant to repressed differentiation genes. We find that this key module of the transcription factor network underlying Ewing's sarcoma is of general importance and not limited to this specific ETS driven neoplasm. Recently, prostate cancer was shown to frequently harbor fusions of the ERG gene. Here we demonstrate that the ETS/E2F3 complex is also present in VCap prostate cancer cells, identify a common set of genes responsive to this module and computationally show that this set of core-responders is involved in proliferation control and translation. Acknowledgement: This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.
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 1285. doi:1538-7445.AM2012-1285
Abstract 1292: Mutually exclusive expression of SOX2 and SOX9 in lung adenocarcinoma cells and its implications
Authors: Jiang Shih-Sheng , Fang Wen-Tsen , Chang I-Shou , Huang Chih-Ting 
Published: August 2012

Abstract
SOX family genes play critical roles in embryonic development, cell fate determination, differentiation, and proliferation. Some members of the SOX family, including SOX2 and SOX9, have been shown as hall marks of lung cancers. However, their roles in lung cancer formation or progression still need to be explored. Here we show an unique expression pattern of SOX2 and SOX9 in lung cancer cells. Using a series of previously established lung adenocarcinoma cell sub-lines which were sequentially selected for increasing cell invasiveness, we found that SOX9 was abundant in highly tumorigenic and invasive sub-lines whereas absent in less tumorigenic and low invasive ones. Interestingly, SOX2 and SOX9 were mutually exclusively expressed among those sub-lines. Forced expression and gene silencing experiments in those cell lines indicated that, while SOX9 is important for cancer cell proliferation, SOX2 is involved in regulation of cell invasion. The involvoed molecular pathways subject to regulations by SOX9 and SOX2 have been partially elucidated and will be demonstrated.
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 1292. doi:1538-7445.AM2012-1292
Abstract 142: Tumor suppressor BRCA1 epigenetically controls oncogenic miRNA-155
Authors: Chang Suhwan , Sharan Shyam 
Published: August 2012

Abstract
BRCA1, a well-known breast and ovarian cancer susceptibility gene with multiple interacting partners, is predicted to have diverse biological functions. However, to date its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate risk variant, and found that it does not impair DNA damage repair but abrogates the repression of miR-155, a bona fide oncomir. We further show that in the absence of functional BRCA1, miR-155 is up-regulated in BRCA1-deficient mouse mammary epithelial cells, human and mouse BRCA1-deficienct breast tumor cell lines as well as BRCA1 mutant tumors. Mechanistically, we found that BRCA1 represses miR-155 expression via its association with HDAC2, which deacetylates H2A and H3 on the miR-155 promoter. Finally, we show that over-expression of miR-155 accelerates whereas the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Taken together, our findings demonstrate a new mode of tumor suppression by BRCA1 and reveal miR-155 as a potential therapeutic target for BRCA1-deficient tumors.
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 142. doi:1538-7445.AM2012-142