bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2102: High resolution fluorescence imaging of cellular DNA and RNA enabled by the synthesis of complex oligonucleotide libraries
Authors: Ach Robert A. , Yamada Alice , Tsang Peter , Pekrun Katja , Scheffer-Wong Alicia , Bruhn Laurakay 
Published: August 2012

Abstract
Fluorescence in situ Hybridization (FISH) is a powerful technique for studying the structure, organization, and localization of nucleic acids within individual cells. However, the use of FISH has often been dependent upon access to cloned template DNA for the generation of probes. Clones for specific regions may be unavailable, or the genomic region of interest may contain repetitive and other non-informative sequences which can be problematic for FISH analysis. We have leveraged our ability to chemically synthesize DNA in massively parallel reactions to produce libraries of oligonucleotides up to 200 bases in length that can be used to generate FISH probes. The sequences of the oligonucleotides in these libraries are selected in silico using empirically determined criteria so as to avoid repetitive elements or regions homologous to other non-targeted loci. Using oligonucleotide library-derived FISH probes on DNA, human genomic regions as small as 1.8 kb and as large as whole chromosomes can be visualized in both metaphase and interphase cells using the same simple assay protocol. Because of the inherent flexibility in our probe design methods, we readily visualized regions rich in repeats and/or GC content. Using oligonucleotide library-derived FISH probes on RNA, we have been able to detect the localization of a variety of both coding and non-coding RNAs in fixed cells, using both conventional fluorescence and structured illumination microscopy. Simultaneous hybridization of FISH probes labeled with different fluorophores enables visualization of multiple sequences at once. Using probes designed specifically to transcribed vs. non-transcribed regions, we have been able to simultaneously detect DNA and RNA from the same locus in the same FISH assay. Our oligo FISH methods are readily compatible with the co-detection of cellular proteins by immunocytochemistry. The ability to generate high performance FISH probes using chemically synthesized oligo libraries that can work flexibly with co-detection of other molecules yields a valuable tool for studies of how localization of specific nucleic acids impacts biological function.
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 2102. doi:1538-7445.AM2012-2102
Abstract 2110: An attempt to replicate the results of genome-wide association studies on lung cancer susceptibility loci in a Korean population
Authors: Kang Hyo-Gyoung , Bae Eun Young , Lee Shin Yup , Jeon Hyo-Sung , Park Jae Yong 
Published: August 2012

Abstract
Genome-wide association studies (GWASs) have identified three chromosomal regions at 5p15, 6p21, and 15q25 as being associated with lung cancer risk in European populations. This study was performed to confirm these associations in Korean patients with lung cancer. The genotypes of rs2736100, rs402710, rs401681, and rs31489 at 5p15, rs9295740 at 6p22, and rs2036534 and rs6495309 at 15q25 were determined in 1094 lung cancer patients and 1100 healthy controls frequency-matched for age and gender. The single nucleotide polymorphisms (SNPs) at 5p15 and 15q25 were significantly associated with lung cancer risk. The magnitude of effect was similar to that reported in previous studies and the association was in the same direction. The effect of SNPs at 5p15 region on the risk of lung cancer was significant only in adenocarcinoma. The two SNPs at 15q25 region were significantly associated with lung cancer risk in ever-smokers and squamous cell carcinoma. However, there was no association between the SNP at 6p22 and lung cancer risk. We confirmed the association between SNPs at the 5p15 and 15q25 regions and the risk of lung cancer in a Korean population.
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 2110. doi:1538-7445.AM2012-2110
Abstract 2115: REV1, DNA polymerase ≤ and the fanconi anemia proteins FANCD2 and FANCI function together during repair
Authors: Sharma Shilpy , Canman Christine E. 
Published: August 2012

Abstract
Fanconi anemia (FA) is a chromosomal instability disorder characterized by bone marrow failure, congenital abnormalities and increased incidence of malignancies. Cells derived from FA patients exhibit cellular hypersensitivity to interstrand crosslink (ICL)-inducing agents, including mitomycin C (MMC) and cisplatin. ICLs are sensed and repaired by a complex process which involves multiple DNA repair proteins including the FA factors as well as proteins that function in nucleotide excision repair, translesion DNA synthesis and homologous recombination (HR). REV1 (a Y family translesion DNA polymerase) and DNA Polymerase ≤ (Polα, comprised of the catalytic REV3 protein and REV7 accessory subunit) play important roles in performing DNA replication across blocking lesions. Previous studies have demonstrated an epistatic relationship between Polα and genes encoding proteins comprising the Fanconi anemia core complex with regards to resistance to ICLs. Additionally, REV1, Polα, and the FANCD2/FANCI heterodimer have each been shown individually to be involved in promoting HR repair, although the reasons for their involvement remain unclear. Here, we show that human REV1 and REV3 exhibit an epistatic relationship with FANCD2 and FANCI in homology-directed repair of a defined DNA double-stranded break and cellular resistance to ICLs created by MMC. We also demonstrate that MMC-induced chromosomal anomalies are increased in REV1 or REV3-depleted cells and FANCD2 depletion does not further exacerbate this phenotype. Additionally, we demonstrate for the first time that full length human REV1 and REV3 interact with FANCD2 and FANCI in vivo as detected by co-immunoprecipitation studies. We therefore propose a model where replication fork stalling during HR repair DNA synthesis is resolved through Polα-dependent translesion DNA synthesis which is regulated by the Fanconi anemia pathway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2115. doi:1538-7445.AM2012-2115
Abstract 212: gp78/AMFR is involved in ubiquitination of PGI/AMF
Authors: Wang Ying , Xie Youming , Nangia-Makker Pratima , Balan Vitaly , Raz Avraham 
Published: August 2012

Abstract
Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) is a multifunctional protein that intracellularly catalyzes the interconversion of glucose 6-phosphate and fructose 6-phosphate in both glycolytic and gluconeogenesis pathways and extracellularly acts as a cytokine associated with aggressive tumor phenotype. Secreted PGI/AMF promotes cancer cell invasion and metastasis by stimulating cell motility via an autocrine manner following binding to its seven-transmembrane glycoprotein receptor gp78/AMFR. Gp78/AMFR also demonstrates an additional function in the endoplasmic reticulum (ER) as ubiquitin ligase (E3). Thus, gp78/AMFR represents a potential link between ubiquitination, ER-associated degradation (ERAD) and metastasis. We questioned if gp78/AMFR is involved in the ubiquitination of PGI/AMF, and whether the ubiquitinated PGI/AMF can be related to cancer progression and metastasis. In this study, we found that indeed PGI/AMF can be ubiquitinated and gp78/AMFR is involved in this process. PGI/AMF was predominantly ubiquitinated via K29-linked ubiquitin chains. Monoubiquitinated PGI/AMF increases the secretion of PGI/AMF and this is the first report to show that monoubiquitinated PGI/AMF is secreted out of the cells. As secretion of PGI/AMF plays a significant role in tumor cell migration and invasion during metastasis, these studies assist in understanding the regulation of PGI/AMF and the mechanisms of its secretion, which may provide a new therapeutic target for tumor metastasis.
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 212. doi:1538-7445.AM2012-212
Abstract 2127: SSB1 is essential for embryogenesis and maintenance of genomic stability in mice
Authors: Khanna KumKum , Shi Wei , Bain Amanda 
Published: August 2012

Abstract
Single-stranded DNA binding proteins (SSBs) are essential for multiple DNA transactions, including regulation of DNA damage checkpoints and repair of DNA damage. Previously, we reported the functional characterization of these proteins in human cells using specific siRNA and provided the initial evidence that both SSBs are essential for efficient repair of DNA double strand breaks by the homologous recombinational repair pathway, and for efficient initiation of the ATM/ATR dependent signaling pathway (Richard et al., 2008). However cellular model systems have inherent limitations. To decipher the role of these newly identified proteins at the organismal level, we have generated conditional SSB1 and SSB2 knockout (KO) mouse models. The constitutive SSB1 KO mice show late embryonic lethality and die perinatally. The conditional inactivation of SSB1 in adult mice is associated with testicular atrophy, reduced fertility and increased genomic instability. We also find compensatory up-regulation of SSB2 protein levels in multiple tissues of conditional SSB1 KO mice. In addition, we report increased radiosensitiity of SSB1-/- mice in response to ionizing radiation, and increased genomic instability, which manifests as a broad spectrum of tumours at approximately 1 year of age. T cells isolated from these animals exhibited mild G1/S and G2/M checkpoint defects, and a persistence of DNA damage as seen by increased gamma-H2AX and 53BP1 foci in response to α-irradiation. Collectively, these results demonstrate an essential role of SSB1 in the maintenance of genomic stability in-vivo. Reference Richard, DJ., Bolderson, E., —et al. Khanna KK (2008). Single-stranded DNA binding protein is critical for genomic stability. Nature 453: 677-681
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 2127. doi:1538-7445.AM2012-2127
Abstract 2143: Smg-GDS regulates cellular proliferation in squamous cell carcinomas of the head and neck
Authors: Bock Jonathan M. , Wrege Kay , Johnston Nikki , Mackinnon Alexander C. , Williams Carol L. 
Published: August 2012

Abstract
Squamous cell carcinoma of the head and neck (SCCHN) is a major worldwide source of morbidity and mortality, with over 26,000 estimated new cases and 6,000 deaths from pharyngeal and laryngeal cancer in 2011 in the the United States alone. SCCHN is an aggressive disease which is characterized by local invasion and lymphatic and distant metastasis. Ras and Rho family GTPases are known to regulate tumor cell proliferation in numerous human cancers including SCCHN. SmgGDS, an unusual guanine nucleotide exchange factor, has previously been shown in other systems to activate these small GTPases and directly regulate cellular proliferation through control of small GTPase prenylation and cellular localization. Little is known about the role of SmgGDS in the progression of SCCHN. These studies were begun to characterize the expression of SmgGDS in SCCHN and assess the role that SmgGDS plays in SCCHN proliferation. SCCHN tumor tissue microarray analysis demonstrated increased SmgGDS expression in tumor tissue from various head and neck sites compared to normal tissues, with evidence for higher SmgGDS expression at the pushing tumor boarders in invasive cancers. Significantly increased amounts of SmgGDS protein and RNA expression were also noted in head and neck tumor cell lines compared to cultured normal head and neck tissue cell lines. To assess the function of Smg-GDS expression in SCCHN, UM-SCC-1 cells were transfected with siRNA directed toward the 60.7 and 55.8 kD SmgGDS isoforms, with significant decreases in S-phase distribution for all treatments. Blocking both 60.7 and 55.8 kD SmgGDS isoforms with siRNA induced an 89% decrease in S-phase distribution as determined by Click-iT Edu cell cycle proliferation assay. These studies confirm an active role for SmgGDS protein function in the promotion of cancer cell proliferation in SCCHN, and provide the basis for further investigations into the role of small GTPases in head and neck neoplasia.
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 2143. doi:1538-7445.AM2012-2143
Abstract 2153: Active PAK6 induces aneuploidy in breast cancer cells
Authors: Lu Michael L. 
Published: August 2012

Abstract
The natural history of breast cancer remains largely undefined. More than 50% of the clinical specimen exhibits aneuploidy. Among these aneuploid cancers, 50% has chromosome copy number near tetraploid. The high incidence of aneupoidy in advanced breast cancer is thought to be a byproduct of chromosome mis-segregation resulting from mutations of checkpoint-regulating tumor suppressor genes associated with disease progression. However, new large-scale sequencing projects reveal that most tumors contain approximately 14-20 different mutant genes, suggesting that genomes and karyotypes of cancer cells are equally heterogeneous. This notion revives the old concept that aneuploidy resulting from chromosome mis-segregation or other similar mechanisms may play an active role leading to transformation and disease progression. A novel p21-activated kinase 6 (PAK6) was recently identified to be an androgen receptor (AR) and estrogen receptor (ER) interacting protein. An estrogen-stimulated PAK6 activation was observed in breast cancer BT474 cells. This activation is mediated by estrogen-stimulated activation of PKA. At the cellular level, active PAK6 promotes breast cancer MCF7 cell metastatic phenotypes including increased cell motility, matrigel invasion and soft agar growth. Further characterization of breast cancer MCF7 cells expressing PAK6 constitutive active mutant revealed an accumulation of cells with higher ploidy as compared to that of parental MCF7. Using a proteomic approach to determine the PAK6 downstream target, we identified that Cdt1, a DNA pre-replicative complex (pre-RC) subunit, is overexpressed in response to PAK6 activation. In eukaryotes, the expression and stability of Cdt1 are strictly regulated to ensure only one round of DNA replication in each cell cycle. Deregulated overexpression of Cdt1 has previously been demonstrated to induce aneuploidy and malignant transformation due to re-initiation of DNA replication within the same S-phase. The identification of Cdt1 overexpression in response to PAK6 activation provides a plausible mechanism for the observed accumulation of higher ploidy cells in MCF7 expressing active PAK6. These findings directly link the hormonal signals to the DNA replication process and maintenance of genomic integrity.
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 2153. doi:1538-7445.AM2012-2153
Abstract 2155: Inhibition of the ERK1/2 pathway by RanBPM
Authors: Atabakhsh Elnaz , Schild-Poulter Caroline 
Published: August 2012

Abstract
Ran binding protein-M (RanBPM, also called RanBP9) is a nucleo-cytoplasmic protein that has been implicated in a multitude of cellular roles, including the regulation of transcription, protein modifications and stability, and extracellular receptor signaling pathways. However its function within the cell remains largely unknown. Previous studies in our lab have identified RanBPM as a pro-apoptotic protein that mediates its effects through modulation of Bcl-2 and Bcl-XL levels. Here we present evidence that RanBPM functions to regulate apoptotic activation through regulation of the ERK1/2 signaling pathway. First, we determined that siRNA-mediated knockdown of RanBPM expression led to elevated Bcl-2 and Bcl-XL mRNA expression, suggesting regulation by RanBPM at the transcriptional level. Additionally, expression of RanBPM affected ectopically expressed Bcl-2 protein levels. Together, these findings suggested that RanBPM regulated the expression of Bcl-2 and Bcl-XL at both the transcriptional and post-translational levels. The ERK1/2 signaling cascade has previously been shown to regulate the expression of Bcl-2 and Bcl-XL at both the transcriptional and post-translational levels. We found that that RanBPM-deficient cells exhibited enhanced ERK1/2 phosphorylation and activation, while re-expression of RanBPM led to a marked decrease in the levels of phosphorylated ERK1/2. Furthermore, enhanced ERK1/2 activation in RanBPM-deficient cells contributed to the elevated levels of Bcl-2 expression observed in these cells, as inhibition of ERK1/2 activation correlated with decreased Bcl-2 protein expression. We characterized regulation of ERK1/2 signaling by RanBPM, and identified that RanBPM targets this pathway downstream of Ras, through modulation of c-Raf stability. Our studies revealed that downregulation of RanBPM expression promotes phosphorylation and stabilization of c-Raf, leading to elevated c-Raf protein expression. Finally we observed that downregulation of RanBPM expression promotes cellular transformation, as RanBPM-deficient cells exhibit increased cell growth rates and enhanced cell migration. Together, these findings suggested that RanBPM acts as a novel inhibitor of ERK1/2 signaling, and that downregulation of RanBPM expression leads to oncogenic transformation.
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 2155. doi:1538-7445.AM2012-2155
Abstract 2161: MLK3 signals to paxillin in chemokine-induced migration and invasion, and is necessary for breast cancer metastasis
Authors: Chen Jian , Gallo Kathleen A. 
Published: August 2012

Abstract
Breast cancer metastasis is the major cause for mortality of patients with invasive breast cancer. Metastasis involves multiple steps including cancer cell invasion through basement membrane, intravasation, survival in the circulation, extravasation and colonization of distant organs. Identification of the signaling pathways through which prometastatic factors promote cancer cell migration and invasion is key to develop effective therapeutics for breast cancer. Mixed lineage kinase 3 (MLK3) is a MAP3K involved in activating each of the three major MAPK signaling pathways. The MLK3-JNK-AP-1 signaling axis has been shown to be required in breast cancer cell migration and invasion. Herein, we demonstrate that the prometastatic factors, CXCL12 and HGF, signal through MLK3-JNK to induce phosphorylation of the focal adhesion scaffold, paxillin on Ser 178, which is required for migration and invasion of human breast cancer cells. Furthermore, we show that MLK3 regulates the phosphorylation of paxillin at Tyr 118 and promotes the interaction of FAK with paxillin, which can be blocked by inhibition of MLK3. To further understand the role of paxillin phosphorylation at S178, a nonphosphorylatable paxillin mutant S178 A was generated. Expression of S178A blocks Y118 phosphorylation of paxillin in breast cancer cells. Silencing of mlk3, inhibition of JNK, or expression of the nonphosphorylatable paxillin S178A increases focal adhesion numbers and increases Rho activity, suggesting that the MLK3-JNK-paxillin axis limits Rho activity in breast cancer cells. Furthermore, MLK3 silencing is sufficient to prevent formation of metastases in a mouse xenograft model of spontaneous breast cancer metastasis. Our findings have identified a novel role of MLK3 in regulation of focal adhesion dynamics and cytoskeletal remodeling in the process of breast cancer cell migration and suggest that MLK3 may be a potential therapeutic target for metastatic breast cancer.
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 2161. doi:1538-7445.AM2012-2161
Abstract 2182: Epigenetic regulation and growth suppression by NDN, an imprinted tumor suppressor gene whose expression is decreased in epithelial ovarian cancers
Authors: Yang Hailing , Das Partha M. , Lu Zhen , Yu Yinhua , Marquez Rebecca T. , Liao Warren , Bast Robert C. 
Published: August 2012

Abstract
NDN is a monoallelically expressed, maternally imprinted gene located on chromosome 15q11.2. Deletion and uniparental disomy of the NDN gene is causally associated with the Prader-Willi syndrome, a congenital neuro-developmental disorder. Studies of brain development suggest that NDN functions as a suppressor of neuronal growth. Recent studies have shown that NDN gene expression is downregulated in melanoma and urothelial cancers, indicating that it may also act as a tumor suppressor gene. We have now found that NDN gene expression is also downregulated in 50% of 14 ovarian tumors and 9 out of 10 ovarian cancer cell lines. Hypermethylation of 2 CpG sites in NDN promoter was detected in 5 out of 10 cell lines by pyrosequencing, and 5-aza-2′-deoxycytidine treatment revived NDN expression at different levels, suggesting that DNA hypermethylation is one of the mechanisms of NDN downregulation. Re-expression of the NDN gene product Necdin in SKOv3 ovarian cancer cells significantly inhibited growth by clonogenic assays associated with upregulation of caspase-3 activity. Expression of Necdin did not induce autophagy. As SKOv3 cells are p53 null, the mechanism(s) by which Necdin induces cell death is independent of p53 activity. Our observations that Necdin expression is downregulated in majority of ovarian cancers and cancer cell lines and that re-expression of Necdin inhibited cancer cell growth support the notion that NDN is a tumor suppressor gene.
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 2182. doi:1538-7445.AM2012-2182