bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1076: Activation of H-Ras and Rac1 correlates with epidermal growth factor-induced breast cell invasion
Authors: Koh Min-Soo , Kim Sun-Young , Lim Do Young , Moon Aree 
Published: June 2012

Abstract
There are considerable experimental evidences that hyperactive Ras proteins promote breast cancer growth and development including invasiveness despite of low frequency of mutated forms of Ras in breast cancer. We have previously shown that H-Ras, but not N-Ras, induces an invasive phenotype mediated by small GTPase Rac1 in MCF10A human breast epithelial cells. Epidermal growth factor (EGF) plays important roles in aberrant growth and metastasis formation of many tumor types including breast cancer. Here, we investigated the involvement of H-Ras in the EGF-induced invasive ability of four different breast cancer cell lines. Upon EGF stimulation, H-Ras activation was increased in the invasive breast cancer cells, MDA-MB-231 and Hs578T cells, but not in non-invasive breast cancer cells, MDA-MB-453 and T47D cells. Using small interfering RNA (siRNA) targeting H-Ras, we showed a crucial role of H-Ras in invasive phenotype induced by EGF in MDA-MB-231 and Hs578T cells. Moreover, knockdown of Rac1significantly inhibited the EGF-induced invasiveness in these cells. Taken together, our data demonstrate that the activation of H-Ras and its downstream molecule Rac1 correlates with breast cancer cell invasion induced by EGF, providing useful information on the regulation of malignant progression in mammary carcinoma. [This work was supported by the Korea government (Nos.ROA-2008-000-20070-0)]
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1076. doi:10.1158/1538-7445.AM2011-1076
Abstract 1084: c-Crk proto-oncogene and TGF-β signaling pathway contribute to transcriptional repression of p120-catenin in non-small cell lung cancer cells
Authors: Mortazavi Fariborz (Fred) , Dubinett Steven M. , Rettig Matthew B. 
Published: June 2012

Abstract
As a member of adherens junction, p120-catenin (p120ctn) plays a major role in cell adhesion through stabilization of E-cadherin. p120ctn is transcriptionally down-regulated in non-small cell lung cancer (NSCLC), although the molecular mechanisms underlying p120ctn repression are incompletely defined. Here we further investigated transcriptional regulation of p120ctn in NSCLC. We prepared a promoter reporter plasmid construct that contained p120ctn promoter region from position -1082 to +320 relative to transcription start site. Through serial deletion mutation analysis of the p120ctn promoter, we pinpointed cis-acting elements involved in regulation of p120ctn. We identified transcription factor SP1 as a transcriptional repressor of p120ctn that directly binds to segment (−9 to +36) of the p120ctn promoter. SP1 can receive multiple signals from several intracellular signaling pathways. Through examination of SP1 binding partners, we identified proto-oncogene c-Crk and TGF-β signaling pathway to be involved in transcriptional down-regulation of p120ctn. RNAi mediated silencing of CRK in A549, H157 and H358 cells increased p120ctn protein levels. On the other hand, over-expression of CRK-I in H358 cells down-regulated p120ctn, an effect that was abrogated by simultaneous silencing of SP1. We also observed that CRK-II serine phosphorylation was inversely correlated with p120ctn expression level. This finding suggests a role for serine/threonine kinases in promoting metastasis through phosphorylation of CRK I/II and subsequently down-regulation of p120ctn. In summary, our data provide evidence for the role of c-Crk proto-oncogene and TGF-β signaling in transcriptional repression of p120ctn that further clarifies the mechanism by which these biochemical signals promote metastasis in NSCLC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1084. doi:10.1158/1538-7445.AM2011-1084
Abstract 109: DNA methylation profiling associated with recurrence of prostate cancer
Authors: Donkena Krishna Vanaja , Klee Eric W. , Young Charles Y.F. , Klee George G. , Tindall Donald J. , Blute Michael L. 
Published: June 2012

Abstract
DNA methylation profiles could signify the risk of prostate cancer and predict the progression of cancer before the appearance of clinical symptoms. Specific CpG sites methylation of genes identified in our study could be used to improve the sensitivity and specificity for early diagnosis and to predict the risk of prostate cancer recurrence. To identify methylation changes associated with prostate cancer, we measured gene methylation using the Infinium Human Methylation27 bead chips. Tissue DNA isolation and bisulfite conversion was done using ZR Genomic DNA kit and EZ methylation kit. The methylation27 microarrays was used to analyze methylation of 27,578 CpG sites of 14,495 genes in 198 tumor tissues and 40 matched normal tissues. Methylation data was processed using the Genome Studio software, differentially methylated genes identified using one-way analysis of variance, and correction for multiple testing done using the false discovery rate q-value. To identify putative diagnostic and prognostic biomarkers we performed four subgroup comparisons: tumor vs. matched normal, recurrent tumors vs. non-recurrent tumors, clinical recurrence vs. biochemical recurrence, and systemic recurrence vs. local recurrence. Clinicopathological and molecular features including patient preoperative PSA levels, Gelason score, TNM stage, GPSM, recurrence type, were also evaluated for subgroup discrimination. Discriminative subgroup candidate methlyation markers were selected using a p value &lt;0.05 and a mean difference between two contrast groups &gt;0.05. Between the tumor and matched normal tissue samples, 164 CpG sites representing 147 genes were identified as significantly differentially methylated (p&lt;9.99E-25, fold change&gt;2.0). Between recurrent tumor and non-recurrent tumor tissues there were 78 CpG sites representing 75 genes that were significantly differentially methylated (p &lt;0.002, fold change &gt;1.5). Between clinically recurrent and biochemically recurrent tumors, 16 CpG sites representing 16 genes were significantly differentially methylated (p &lt;0.05, fold change &gt;1.5). Between systemic recurrent and local recurrent tumors there were 73 CpG sites representing 68 genes that were significantly differentially methylated (p &lt;0.01, fold change &gt;1.5) Our analysis revealed differential methylation of the genes, implicating their role in prostate cancer development and progression. We demonstrated that the hypermethylation of genes could be used as a sensitive molecular tool in detection of prostate tumorigenesis and prediction of tumor progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 109. doi:10.1158/1538-7445.AM2011-109
Abstract 1093: BioMAP® profiling in primary human cell systems as a tool for drug discovery in inflammation and cancer
Authors: O'Mahony Alison M. , Melrose Jennifer , Privat Sylvie , Alajoki Liisa , Nguyen Dat , Polokoff Mark , Plavec Ivan , Berg Ellen 
Published: June 2012

Abstract
It is now widely accepted that chronic inflammatory events are critical contributors to both the development and progression of cancer. While the complex interrelationship between immune events and their effects on the neoplastic process remain to be defined, targeting inflammation has now become a priority of drug discovery in oncology. A major factor propelling this strategy is that both cancer cells and immune cells share many common signaling pathways that can contribute to the disease promoting microenvironment of the tumor. Drugs that target these pathways now make up a significant portion of pharmaceutical pipelines but how these compounds affect cancer cells, normal tissues and immune processes remains poorly understood. In order to develop more effective therapeutic strategies it is imperative that we understand the biological impact of compounds that target key signaling intermediates on normal and immune cells as well as neoplastic cells. BioSeek has pioneered the development of in vitro human cell-based systems (BioMAP® Systems) that recapitulate the complex signals and phenotypic responses of inflamed tissues in vivo. In addition to providing broad coverage of inflammatory targets, BioMAP® Systems model modulation of many signaling pathways relevant to cancer. Characterization of pathway-associated kinase inhibitors, including JAK, PI3K, p38MAPK, ERK, JNK and NF-κB in BioMAP® Systems has revealed activities that differentially impact inflammatory, proliferative, angiogenic and tissue remodeling processes. Secondly, profiling of 1000s of off-patent compounds through BioMAP® Systems identified agents that selectively prevent the growth of smooth muscle cells and related cancers (leiomyosarcomas and rhabdomyosarcomas) with little impact on the activation of immune cells. BioMAP® Systems provide a highly useful platform to (1) distinguish anti-inflammatory and anti-proliferative effects of various kinase inhibitors and (2) identify different phenotypic outcomes of these agents that influence cancer progression and disease resolution. Together these data will help inform the selection of more effective therapeutic strategies to target different cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1093. doi:10.1158/1538-7445.AM2011-1093
Abstract 1096: Prostate tumor growth in pbARR2-Cre PTEN knockout mice is delayed in GH/IGF-I deficient mice
Authors: Ibuki Naokazu , Takahara Kiyoshi , Tearle Howard , Gleave Martin E. , Ong Christopher J. , Pollak Michael , Cox Michael E. 
Published: June 2012

Abstract
Growth hormone/insulin-like growth factor I (GH/IGF-I) axis has been related to risk of prostate cancer (PCa). We have previously reported that androgen-responsive, castration-resistant (CR), and androgen-independent (AI) PCa xenografts develop more slowly in little murine hosts. The little (lit/lit) phenotype is due to a D60G missense mutation in the GH-releasing hormone receptor (GHRHR) resulting in loss of pituitary GHRHR function and suppression of GH and IGF-I expression. PTEN is a tumor suppressor gene that is frequently mutated in a variety of spontaneous cancers, including PCa. The prostate-conditional PTEN-null mouse represents the first animal model in which deletion of a single endogenous gene leads to invasive PCa. To investigate the role of GH/IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we crossed pbARR2-Cre, PTEN(fl/fl) mice (PTEN-/-) with IGF-I deficient lit mice, and produced lit/lit and lit/+ PTEN-/- mice. To complement the in vivo experiments, in vitro growth and growth factor signaling of murine PTEN-/- cells derived from the prostate (MPPK) or lymph node (MLPK) using serum from lit/lit or lit/+ mice was examined. RESULTS: Body weight and serum GH, IGF-I levels of lit/lit PTEN-/- mice were significantly reduced as compared with lit/+ PTEN-/- mice. At 15 weeks of age, prostate cancer progression of lit/lit PTEN-/- mice was partially delayed as compared with lit/+ PTEN-/- mice. MPPK and MLPK cells growth in vitro with serum from lit/lit mice showed decreased proliferation as compared with serum from lit/+ mice. Suppressed growth in lit/lit serum could be restored by addition of IGF-I, and to a lesser extent, GH. Addition of GH or IGF-I to lit/lit serum increased only activation of AKT while no change in ERK1/2 activation was detected in MPPK cells. Our in vivo and in vitro results suggest that prostate carcinogenesis may be influenced by germ line variation of genes encoding signaling molecules in the GH/IGF-I axis and support the continued development of clinical trials of novel hormonal treatment strategies that target the GH/IGF-I axis for PCa patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1096. doi:10.1158/1538-7445.AM2011-1096
Abstract 1100: Correlation of basic fibroblast growth factor and cyclooxygenase-2 activity in non-small lung cancer cells
Authors: Fulson-Woytek Michael J. , Valenta David A. , Baguma-Nibasheka Mark 
Published: June 2012

Abstract
Basic fibroblast growth factor (FGF-2) is a potent wide-spectrum mitogen and the dysregulation of its expression is associated with cell proliferation and immortalization in a wide variety of tumors. Its oncogenic nature may depend, in part, on its ability to prevent apoptosis. Its antisense gene, NUDT6, encodes a novel Nudix motif protein of unknown function, and overexpression of NUDT6 is known to suppress FGF-dependent cell proliferation (Baguma-Nibasheka et al, Mol Cell Endocrinol 267:127-136, 2007). Cyclooxygenase-2 (COX-2) is a key enzyme in prostaglandin synthesis whose up-regulation has been implicated in the promotion of lung cancer. COX-2 inhibition suppresses growth and induces apoptosis in human non-small cell lung cancer (NSCLC) cells. In this study, we evaluated the hypothesis that the antitumor activity of COX-2 inhibitors in lung cancer may involve modulation of FGF-2, which is overexpressed in NSCLC. Results: FGF, NUDT6 and COX-2 are co-expressed in NSCLC cells, and FGF-2 and COX-2, but not NUDT6 messenger RNA levels, as well as cell proliferation, are decreased by serum deprivation. Selective inhibition of COX-2 suppresses FGF-2 but not NUDT6 expression, and FGF-2 knockdown negates the effect of COX-2 inhibition on cell proliferation. These findings indicate that the antitumor effects of COX-2 inhibition in NSCLC may be mediated via suppression of FGF-2. Supported by the Frostburg State University of Biology Department.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1100. doi:10.1158/1538-7445.AM2011-1100
Abstract 1103: Expression profile and role of thromboxane synthase in NSCLC: Correlation with tumor angiogenesis and patient survival
Authors: Cathcart Mary-Clare , Gately Kathy , Kay Elaine , Reynolds John V. , O’ Byrne Kenneth J. , Pidgeon Graham P. 
Published: June 2012

Abstract
Introduction: Thromboxane synthase metabolizes PGH2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression is frequently reported in cancers, and has previously been associated with VEGF and a poor prognosis. TXS blockade inhibits angiogenesis and induces tumor cell death, providing a rationale for intervention. This study aimed to determine the expression profile of TXS, its link to tumor angiogenesis, and if it is prognostic and/or a survival factor in NSCLC.
Methods: TXS expression was examined in human NSCLC samples (protein and tissue) and matched controls by western analysis and IHC. TXS metabolite levels were measured in human NSCLC plasma samples and age-matched controls by EIA. TXS metabolite levels were correlated with VEGF. A 200-patient NSCLC TMA was stained for TXS, VEGF, and CD-31. Staining was correlated with clinical parameters, including 5-year patient survival. TXS expression pattern was correlated with angiogenic markers, VEGF and CD-31 (microvessel density). Stable TXS over-expressing clones were generated and their effect on tumor growth was examined both in-vitro (BrdU) and in-vivo (xenograft mouse model).
Results: TXS was over-expressed in human NSCLC samples, relative to matched controls. Increased TXS and TXB2 levels were observed in protein and plasma samples respectively. TXB2 levels were significantly (p&lt;0.05) correlated with VEGF, while both TXB2 and VEGF levels were higher in adenocarcinoma. Both TXS and VEGF tissue expression were also significantly higher in adenocarcinoma (p&lt;0.001) and female patients (p&lt;0.05). TXS tissue expression was also significantly correlated with that of VEGF (p&lt;0.0001) and CD-31. However, no correlation of TXS with patient survival was observed. Stable TXS over-expression significantly increased tumor cell growth in-vitro and also increased tumor growth in-vivo.
Conclusion: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype and female patients. While TXS was not found to be prognostic, over-expression of this enzyme significantly increased tumor growth both in-vivo and in-vitro, suggesting that TXS promotes tumor survival in NSCLC. Our study also demonstrated a significant correlation of TXS with both VEGF and tumor vessel count, suggesting that the pro-tumor effects of TXS expression are at least partly mediated via tumor angiogenesis. Further studies using in-vivo models will confirm this observation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1103. doi:10.1158/1538-7445.AM2011-1103
Abstract 1107: Transforming growth factor-beta (TGF-β) increases Par-4 expression via activation of Smad and NF-κB in endometrial cancer cells
Authors: Singh Mohan , Chaudhry Parvesh , Asselin Eric 
Published: June 2012

Abstract
Prostate apoptosis response-4 (Par-4) gene was originally identified in prostate cancer cells undergoing apoptosis. Further studies have shown that Par-4 selectively induces apoptosis in cancer cells without effecting normal cells. Recently it has been evidenced that Par-4 has a tumor suppressor role in endometrial cancer. We have previously demonstrated that TGF-β isoforms are expressed in endometrial tumors and determined cellular fate by regulating apoptosis through the activation of NF-κB. In the present study, we have investigated the mechanisms through which TGF-β isoforms regulate Par-4 expression in endometrial cancer cells. KLE and Hec-1-A endometrial cancer cell lines were used as model in this study. Transcript and protein levels were assessed by reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting, respectively. The results revealed that both cell lines express TGF-β receptor I and receptor II. Blocking TGF-β signalling by neutralizing TGF-β antibody reduced endogenous Par-4 mRNA and protein levels. Exogenous treatment with all the TGF-β isoforms (10ng/ml) upregulated Par-4 mRNA and protein levels. Furthermore, there was increase in the levels of phosphorylated Smad2 and Smad3 in response to TGF-β treatment, thus indicating that Smad pathway was activated by TGF-β isoforms in these cells. However, there was no change in the protein levels of total Smad2/3. TGF-β treatment resulted in rapid phosphorylation of IκB-α with no effect on total IκB-α levels thus suggesting an activation, nuclear translocation and increase in transcriptional activity of NF-κB. Collectively, these results suggest that each TGF-β isoform induces Par-4 levels via the activation of Smad and NF-κB pathway in endometrial cancer cells. Since downregulation of Par-4 is a common event in different types of cancers, we suggest in these cases that TGF-β could be an interesting therapy and strategy to induce Par-4 and apoptosis in endometrial cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1107. doi:10.1158/1538-7445.AM2011-1107
Abstract 1108: Ferritin binds breast cancer cells and tissue, and promotes proliferation independently of iron content
Authors: Alkhateeb Ahmed , Connor James 
Published: June 2012

Abstract
A connection between iron and breast tumorigenesis has been convincingly argued over the years. Several in vivo studies have demonstrated that iron-rich diets increase tumor incidence rate in carcinogen-induced mammary tumor models. Moreover, a large cohort study has recently associated mutations in the hemochromatosis (HFE) gene (promoting iron overload) with breast cancer risk in females. Individuals with mutations in the HFE protein can exhibit iron accumulation in the liver, high transferrin saturation levels, and elevated serum ferritin levels, but not have clinical hemochromatosis.
Cells store iron in ferritin, but this protein is also secreted and is detected circulating in serum. Although serum ferritin has been used as an indicator of total body iron, a specific functional role has not been proposed thus far other than perhaps recycling iron to the bone marrow. Interestingly, serum ferritin levels have been shown to be increased in breast cancer patients, and higher levels seem to be associated with poorer prognosis. Furthermore, comparisons between pre- and post-surgery ferritin levels suggested that the tumor itself is responsible for the high levels of serum ferritin possibly through secretion. We have demonstrated that ferritin binds to breast tumor sections obtained from biopsy. Based on these observations, we hypothesized that serum ferritin interacts directly with breast cancer cells enhancing their growth. In this study we report that ferritin exposure will increase proliferation and DNA synthesis in the breast cancer cell lines, MCF-7 and T47D. These effects were not dependent on the iron content of ferritin, as both apo- and holo-ferritin had comparable effects. Because extra-cellular ferritin has been speculated to play an iron delivery role in some cells, we examined changes in transferrin receptor levels, and the quenching of the fluorescent metal-sensitive dye calcein following ferritin treatments. Our data, suggests that ferritin does not deliver iron to cells, and might have an iron-independent signaling function. Taken together, these findings encourage a new perspective on serum ferritin in cancer biology, and raise several possibilities for novel therapeutic and diagnostic strategies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1108. doi:10.1158/1538-7445.AM2011-1108