bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3966: 14-3-3 sigma and 14-3-3 zeta plays an opposite role in cell growth inhibition mediated by transforming growth factor-beta 1
Authors: Hong Hye-Young , Jeon Woo-Kwang , Park Sung-Ji , Jang Hyung-Ju , Choi Ji-Yeon , Kim Byung-Chul 
Published: February 2011

Abstract
The expression of 14-3-3 proteins is dysregulated in various types of cancer. This study was undertaken to investigate the effects of 14-3-3 ζ and 14-3-3 σ on cell growth inhibition mediated by transforming growth factor-beta 1 (TGF-β1). Mouse mammary epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-β1-mediated growth inhibition displayed increased expression of 14-3-3 ζ and decreased expression of 14-3-3 σ compared with parental Eph4 cells. Using small interfering RNA-mediated knockdown and overexpression of 14-3-3 σ or 14-3-3 ζ, we showed that 14-3-3 σ is required for TGF-β1-mediated growth inhibition whereas 14-3-3 ζ negatively modulates this growth inhibitory response. Notably, overexpression of 14-3-3 ζ increased the level of Smad3 protein that is phosphorylated at linker regions and cannot mediate the TGF-β1 growth inhibitory response. Consistent with this finding, mutation of the 14-3-3 ζ phosphorylation sites in Smad3 markedly reduced the 14-3-3 ζ-mediated inhibition of TGF-β1-induced p15 promoter-reporter activity and cell cycle arrest, suggesting that these residues are critical targets of 14-3-3 ζ in the suppression of TGF-β1-mediated growth. Taken together, our findings indicate that dysregulation of 14-3-3 σ or 14-3-3 ζ contributes to TGF-β1 resistance in cancer cells.
Following are results of a study on the “Human Resource Development Center for Economic Region Leading Industry” Project, supported by the Ministry of Education, Science & Technology(MEST) and the National Research Foundation of Korea(NRF)
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 3966.
Abstract 3972: The role of the TGF-β type III receptor in colon carcinogenesis
Authors: Holtzhausen Alisha , Gatza Catherine E. , Kirkbride Kellye C. 
Published: February 2011

Abstract
The loss of the TGF-β type III receptor (TβRIII), a TGF-β superfamily co-receptor, correlates with disease progression in multiple cancer types, suggesting that TβRIII plays a role in regulating tumor progression. TGF-β superfamily signaling is frequently dysregulated in colon cancer but the specific role of TβRIII in colon carcinogenesis has not been examined. In contrast to other cancer types, TβRIII mRNA expression is not altered in colon cancer and there is not a significant change in TβRIII protein expression in tumors compared to normal colon tissue. HT29 colon cancer cells overexpressing TβRIII (HT29-RIII) exhibit an increase in proliferation in response to TGF-β and BMP2 stimulation compared to HT29-Neo cells. This increase in proliferation is mediated through the down-regulation of p21. In a soft agar assay HT29-RIII cells demonstrate increased colony formation in response to ligand treatment. Additionally, HT29-RIII cells are resistant to anoikis and 5FU-induced apoptosis. Colon cancer cells expressing TβRIII also exhibit increased migration potential and this increase in migration can be abrogated by knockdown of TβRIII expression. Furthermore, cells over-expressing TβRIII show alterations in E-cadherin and actin organization. Taken together, these data suggest that TβRIII may have a pro-tumorigenic role in colon cancer tumorigenesis as it mediates ligand stimulated proliferation, resistance to apoptosis and increased migration. Further work is currently underway to more fully elucidate the role of TβRIII in colon cancer progression in vitro and in vivo.
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 3972.
Abstract 3977: Gene-expression signature specifically associated with triple-negative breast cancer pertaining to asian ethnicity
Authors: Chang Yao-Yin , Kuo Yu-Ho , Chen Hung Lee , Lai Liang-Chuan , Kuo Wen-Hung , Hsiao Chuhsing Kate , Chuang Eric Y. , Chang King-Jen 
Published: February 2011

Abstract
Triple-negative breast cancer is a subtype of breast cancer with strong aggressiveness of tumor behavior and distinct patterns of metastasis. This unique phenotype of breast cancer is given by its clinically negative expression of estrogen receptor (ER), progesterone receptors (PR), and HER2 protein. Triple-negative breast cancer patients often suffer from ineffective hormone therapies, high recurrence rate, and a predilection for visceral metastasis. An accurate gene-expression signature specifically associated with triple-negative breast cancer will facilitate the identification of the existence of this disease and provide insights of its etiology.
DNA microarray analysis was used to evaluate gene-expression profiles of 181 Asian breast cancer patients. There were 48 breast cancer patients who were triple-negative, and 133 of them were non-triple-negative. Several clinical information were matched in each group, including lymphovascular invasion, age, stage, grade, tumor size, tubule formation, nuclear pleomorphism, and mitotic count. After all 181 microarray data were normalized with quantile normalization, significantly expressed genes differentiated from the triple-negative group and non-triple-negative group were extracted using SAM (Significant Analysis of Microarray) and T-test. A panel of 50 genes was selected as the gene-expression signature for triple-negative breast cancer for Asian ethnicity, based on their unique patterns of gene-expression data using hierarchical clustering. Pathway analysis of the signature genes for triple-negative breast cancer was then performed in the lab. Genetic interactions of significantly expressed genes among different pathways found in this study will be shown and elaborated on the poster.
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 3977.
Abstract 3993: Characterisation of early ovarian cancer biomarkers
Authors: Meehan Katie L. , Rainczuk Adam , Fairweather Nicole , Stephens Andrew 
Published: February 2011

Abstract
Around 22,000 new cases and 15,500 deaths from ovarian cancer are expected in the US in 2008, and currently women run an estimated 1/67 risk of developing ovarian cancer during their lifetime. Approximately 70% of patients present with late stage disease (stages III - IV; FIGO classification) and have a poor prognosis, with only a ∼30% 5 year survival rate. By contrast, patients diagnosed with early (stage I) disease exhibit survival rates above 90%, with disease often cured by surgery alone. The key issue is that early detection is hampered by a lack of sensitive and specific markers. The aim of this ongoing study was to apply 8-plex isobaric tags for relative and absolute quantitation (iTRAQ) for the proteomic investigation for early stage markers of ovarian cancer.
Plasma was collected from patients and pooled as follows: G1-early stage cancers (stage I/II), G2-late stage cancers (stage III), G3-ascites fluid, G4-benign adenomas, G5-benign adenofibromas, G6-controls and G7-pool of all samples. Pooled patient samples were immuno-depleted of 12 abundant, disease-unrelated proteins and concentrated using reverse phase chromatography. Equal protein concentrations of each of the 7 pools were reduced, denatured, alkylated and digested using trypsin. Peptides from G1 through G7 were labelled with iTRAQ labels −113 to −119 respectively. Samples were combined and analysed using two-dimensional liquid chromatography (2D-LC) and mass spectrometry (4700 MALDI-TOF/TOF or QStar Elite, Applied Biosystems). Data were analysed using Protein Pilot (version 3.0, Applied Biosystems).
Initial studies have identified 111 proteins with quantitation of 71 proteins, including numerous proteins that have been patented as candidate early markers for ovarian cancer. Of those identified, many are involved in inflammation/immunity and coagulation. Of considerable interest was the quantitative identification of numerous low abundance proteins not previously associated with early stage ovarian cancer.
This proteome analysis has generated a catalogue of proteins that display potential as early markers for ovarian cancer. In addition, this study will assist in our understanding of the pathways potentially involved in the onset and progression of ovarian 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 3993.
Abstract 3999: Human proteome arrays for auto-antibody identification in clinical cancer studies
Authors: Kenten John H. , Suschak Jessica , Roth Kristian , Jeffery-Coker Bandele , Yin Fei , Glezer Eli N. 
Published: February 2011

Abstract
Early detection, identification and classification of cancers still present considerable challenges. Innovations in several areas of research have provided novel and powerful approaches with which to tackle these challenges. Autoantibodies to tumor antigens have been found in cancer patients. Such autoantibodies are potentially ideal diagnostic biomarkers, as they are present in serum, are stable, and can be measured using established serological techniques. In order to discover new autoantibody responses in cancer patients, we have developed an approach based on the generation of protein arrays for systematic identification of auto-reactive antibodies. Our approach makes use of several key technologies: sequence-curated clone libraries, in-vitro protein expression, and a sensitive detection technology based on a proprietary combination of electrochemiluminescence detection and patterned arrays (Multi-Array® Technology, Meso Scale Diagnostics). Using this combination of technologies we plan to generate immobilized arrays of &gt;1,000 proteins, with a high density of proteins per well in a 96-well microtiter plate format. The array of human proteins is selected from our collection of 60,000 mammalian clones (characterized by sequencing). The protein arrays will be used to screen cancer patient sera and controls.
During the initial development of this platform we optimized the protocols for in-vitro protein expression and labeling, specifically for immobilization on our Multi-Array plates. With this approach we have demonstrated detection of antigen-specific antibodies down to a concentration of 0.1 ng/mL. We have also validated this approach in a model system, with the detection of auto-reactive antibodies in the sera from 29 patients with a range of auto-immune diseases (Sjogren's syndrome, mixed connective tissue disease, scleroderma, systemic lupus erythematosus, and primary bilary cirrhosis), using 9 cloned autoimmune antigens. In parallel, we also optimized approaches for spotting in-vitro expressed proteins in high density spot/well arrays. In these studies we evaluated a selection of electrode surfaces and protein coupling methods, in combination with various spotting methods, and demonstrated serological measurements in a high density spot/well array. This effort was supported with funding from the NCI #1R44CA130391-1A1.
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 3999.
Abstract 4006: Soluble ALK4 extracellular domain antagonizes oncogenic Cripto signaling and inhibits tumor growth
Authors: Spike Benjamin T. , Kelber Jonathan A. , Booker Evan C. , Klemke Richard L. , Wahl Geoffrey M. , Vale Wylie W. , Gray Peter C. 
Published: February 2011

Abstract
Cripto is a small GPI-anchored glycoprotein that plays key roles during normal development and in tumorigenesis. Cripto is expressed at aberrantly high levels in human tumors and blocking its oncogenic effects on activin/Nodal/TGF-beta, Erk/MAPK and PI3K/Akt pathways represents a promising therapeutic strategy. Cripto functions as a Nodal co-receptor and binds directly to the extracellular domain (ECD) of the activin/Nodal type I receptor ALK4. We have shown that a kinase-deleted ALK4 mutant deficient in activin binding (ALK4-L75A) retains Cripto binding and can block Cripto effects on activin and Nodal signaling. We hypothesized that soluble ALK4-L75A ECD proteins would similarly bind Cripto and disrupt oncogenic Cripto function. To test this, we generated two soluble constructs incorporating the ALK4-L75A ECD, one with a C-terminal His tag (sALK4-L75A-His) and the other consisting of an ALK4-L75A ECD-Fc fusion with an N-terminal FLAG tag (sALK4-L75A-Fc). We expressed the sALK4-L75A-His and sALK4-L75A-Fc proteins in 293T cells and then purified them from conditioned media using Ni-NTA agarose and Protein-A agarose, respectively. The sALK4-L75A-Fc protein dose-dependently inhibited 125I-Cripto binding to 293T cells transfected with full length ALK4. In addition, sALK4-L75A-Fc blocked 125I-Cripto binding to untransfected human mammary epithelial MCF10A cells. In accordance with these binding data, sALK4-L75A-His inhibited Cripto-dependent Nodal signaling in 293T cells and sALK4-L75A-Fc inhibited Nodal-induced Smad2 phosphorylation in human NCCIT cells. sALK4-L75A-His also blocked Cripto-induced PI3K signaling while sALK4-L75A-Fc inhibited Cripto-induced MCF10A cell proliferation. Importantly, we have shown that sALK4-L75A-Fc can also inhibit the growth of tumor xenografts derived from NCCIT cells at doses where no toxicity was observed. Thus, we provide the first evidence that soluble forms of ALK4 inhibit oncogenic Cripto signaling. The efficacy of a soluble ALK4 receptor as an antitumor agent points to the utility of Cripto antagonists in the treatment of human 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 4006.
Abstract 4007: Cooperative regulation of Stat3 signaling by TC-PTP, SHP1, and SHP2 in keratinocytes following UVB irradiation
Authors: Kim Dae Joon , Tremblay Michel L. , DiGiovanni John 
Published: February 2011

Abstract
Stat3 is initially dephosphorylated in murine keratinocytes in response to UVB irradiation. Treatment with Na3VO4 desensitized keratinocytes to UVB-induced apoptosis with the recovery of phosphorylated Stat3 protein levels, implying that a protein tyrosine phosphatase (PTP) is involved in this mechanism. In the current work, we report that three PTPs including TC45, the nuclear form of TC-PTP, SHP1, and SHP2 are involved in this rapid dephosphorylation of Stat3 in keratinocytes induced by UVB irradiation. Dephosphorylation of Stat3 was increased rapidly after UVB irradiation of cultured keratinocytes. Knockdown of TC-PTP, SHP1, or SHP2 using RNAi showed that these PTPs are in part responsible for Stat3 dephosphorylation following UVB irradiation. The level of phosphorylated Stat3 was significantly higher in keratinocytes transfected with TC-PTP, SHP1, or SHP2 siRNA in the presence or absence of UVB compared with keratinocytes transfected with control siRNA. TC45, the isoform of TC-PTP expressed in keratinocytes, was mainly localized in the cytoplasm of keratinocytes and translocated from cytoplasm to nucleus upon UVB irradiation. Stat3 dephosphorylation was associated with nuclear translocation of TC45. Further studies revealed that simultaneous knockdown of all three phosphatases, TC45, SHP1, and SHP2, using RNAi recovered the level of phosphorylated Stat3 upon UVB irradiation. In mouse epidermis, the level of phosphorylated Stat3 also was initially decreased by UVB irradiation followed by a significant increase at later time points after UVB exposure. The expression patterns of Stat3 target genes, such as cyclin D1 and c-Myc, followed the changes in activated Stat3 in response to UVB irradiation. Collectively, these results suggest that three phosphatases, TC45, SHP1, and SHP2, are responsible for UVB-mediated Stat3 dephosphorylation and may serve as part of an initial protective mechanism against UV skin carcinogenesis. Supported by NIH grants CA105345, CA76520 and an Odyssey Fellowship to DJK.
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 4007.
Abstract 4016: Large scale, domain-based comparative protein interaction mapping in cancer cell signaling
Authors: Hindie Valerie , Tafelmeyer Petra , Meil Alain , Collura Vincent , Hamburger Alexandre , Wojcik Jérôme , Barillot Emmanuel , Boissy Guillaume , Camonis Jacques , Daviet Laurent , Formstecher Etienne 
Published: February 2011

Abstract
Protein interaction mapping has proven instrumental for the delineation and understanding of cancer signaling pathways, both in Homo sapiens and model organisms. We have recently published a drosophila protein interaction map centered on fly orthologs of human cancer-related and signaling proteins1.
We now report the completion of the cognate human interaction map using the same high-throughput, domain-based yeast two-hybrid (Y2H) technology. 149 human homologs of the 102 drosophila proteins, including 29 human oncogenes and tumor suppressors2, were used as entry points to screen a highly complex, random-primed placenta cDNA library comprised of 10 million independent fragments in yeast. In order to strictly parallel the drosophila study, the same domains were selected as baits on human orthologs, resulting in 230 different screens. To ensure reproducible and exhaustive Y2H results, the library was screened at saturation using an optimized mating procedure that allowed for testing on average 50 million interactions per screen, corresponding to a 5-fold coverage of the library. As a consequence, multiple, independent fragments of the same interactant could be isolated, enabling the delineation of a minimal interacting domain and the computation of a confidence score.
We identified 4,089 protein-protein interactions (PPI) connecting 2,412 human proteins. 1,212 PPI (30%) are of high confidence and connect 998 proteins. Interestingly, 54 additional human oncogenes or tumor suppressors were identified in the screening, and a sub-network of 1089 PPI linking at least one cancer protein was derived from the full map. The features of the drosophila and human parallel interaction maps were compared. Orthology relationships were combined with Y2H data and the conservation of interaction networks across evolution was examined. Experimentally determined interacting domains were also systematically confronted to known functional domains in both species, pointing to a significant enrichment of domains involved in protein binding. Finally, both experimental protein interaction maps were extended by including protein interaction data from the literature. We believe that this protein interaction map centered on human cancer signaling pathways will be an invaluable resource for researchers in the field.
References :
1. Formstecher et al., 2005, Genome Research, 15:376
2. Futreal et al., 2004, Nature Review Cancer, 4(3):177
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 4016.
Abstract 4028: A consolidated microplate-based workflow for monitoring intracellular calcium mobilization and mitochondrial membrane potential changes
Authors: Shen Dee , Patton Wayne 
Published: February 2011

Abstract
The interactions between mitochondrial function and Ca2+ homeostasis are very complex. Mitochondria are known to serve as dynamic calcium storage compartments, and also form intimate contacts with other calcium-handling organelles, such as the endoplasmic reticulum. Calcium enters mitochondria, not only during pathological processes, but also during physiological calcium responses. This organelle does not simply passively buffer excessive calcium but actively utilizes calcium signals to regulate integral cell activities, such as oxidative phosphorylation and the Kreb's cycle. A consolidated microplate-based workflow is described for assessing the relationship between mitochondria and global calcium responses. Two novel small molecule probes were implemented in the assay. Mitochondrial membrane potential was monitored using a dual-emission fluorescent probe that is roughly 10-25-fold more sensitive than the conventional carbocyanine dye, JC-1. Calcium mobilization was examined using a novel fluorescent calcium indicator dye that is significantly brighter than Fluo-4 AM dye. The assay is readily performed using a fluorescence microplate reader equipped with a dual-reagent dispenser. Proof-of-principle studies were performed by evaluating cell response to two agents, diazoxide, a putative opener of the potassium-ATP channel, and BML-258, a novel sphingosine kinase-1 inhibitor. The assay workflow is suitable for monitoring calcium mobilization and mitochondrial membrane potential changes across a broad spectrum of biological targets. The easy-to-use protocol is automation-friendly and can be performed in a convenient 96-well or 384-well microplate format. The assay should provide insight into the interaction between calcium signaling and mitochondrial energetic status, relevant to a range of phenomena, including ischemia/reperfusion injury. It should also serve as a high-throughput approach for identifying specific small molecule pharmacological agents targeted to this complex interrelationship.
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 4028.