bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 329: Identification of the breakpoints of two chromosome translocations involving chromosomes 4 and 7 observed in two murine mammary carcinomas
Authors: Pampena María B. , Merani Susana , Lanari Claudia , Fabris Victoria T. 
Published: February 2011

Abstract
The translocation between chromosomes 4 and 7, T(4;7), was observed in two different mammary carcinomas from the medroxyprogesterone acetate (MPA) mouse breast cancer model which have acquired a hormone independent (HI) phenotype (C7-2-HI and C4-HI). We had developed a cell line from the C7-2-HI tumor, the MC7-L2A cells, which retain the chromosome translocation T(4;7), and provide an easy tool to obtain metaphases. G-banding analysis showed that the breakpoint on chromosome 4 is located on the band 4E in the C7-2-HI tumor, whereas in the C4-HI tumor, it is located on the region 4C4-4D3. However, the breakpoint on chromosome 7 is located near the centromere in both tumors. Further experiments using fluorescence in situ hybridization (FISH) in MC7-L2A cells have shown that the breakpoint of the translocation involved the chromosome bands 4E2 and 7A1-A2. The aim of this project is to elucidate whether these breakpoints are involving new gene rearrangements that might participate in the acquisition of hormone independency. In this study we focused in determining if the break in chromosome 7 is located on the same band in both HI tumors. A detailed analysis in MC7-L2A cells using FISH with different DNA probes, spanning the region 7A1-7A2, showed that the breakpoint is located on chromosome 7A1 and not on band 7A2. However, a different picture was observed in metaphases obtained from C4-HI tumor cells, in which the probes corresponding to region 7A1-7B1 hybridized only to normal chromosome 7, but not to the translocation T(4;7). These results indicate that the breakpoints on chromosomes 4 and 7, although involving the same chromosomes, are located on different regions in the T(4;7) translocations, suggesting that they may be random breakpoints. Even though we could not associate this breakpoint with the hormone-independent phenotype, the identification of the sites of chromosome breaks may be relevant to understand the biology of each HI tumor.
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 329.
Abstract 3291: Upregulation of Insulin Receptor Substrate-2 (IRS-2) expression by hypoxia
Authors: Mardilovich Katerina , Shaw Leslie M. 
Published: February 2011

Abstract
Insulin Receptor Substrate-2 (IRS-2) belongs to the IRS family of cytoplasmic adaptor proteins that mediate signaling from cell surface receptors, including growth factor, cytokine and integrin receptors. Many of these receptors have been implicated in cancer. Although the IRS proteins are highly homologous in structure and have some complementary functions, growing evidence supports that the IRS proteins have unique roles in cancer. IRS-1 has been shown to promote tumor cell proliferation, while IRS-2 has been positively associated with tumor cell motility and invasion. Previously, our lab demonstrated that Polyoma Middle T-derived Irs-2−/− mouse mammary tumors are significantly less metastatic, and Irs-1−/− tumors significantly more metastatic, than their wild-type counterparts. In recent studies, we observed that IRS-2 expression increases in response to hypoxia in both metastatic mouse mammary tumor cells and poorly differentiated ER-negative metastatic human breast carcinoma cells. In contrast, IRS-1 expression does not increase in response to hypoxia, supporting the notion of their non-overlapping functions. Hypoxia promotes the adaptation and resistance of cancer cells to chemo- and radiation therapy, and also promotes tumor cell survival, invasion and metastasis by selecting for aggressive tumor cells that can survive under stressful low oxygen conditions. We have also shown that IRS-2 upregulation in response to hypoxia promotes tumor cell viability and invasion, selecting for tumor cells with increased metastatic potential. To understand how IRS-2 is regulated by hypoxia, we identified a minimal 200 bp region of the IRS-2 promoter located 700 bp upstream from the translation start site that is hypoxia-responsive. Mutation of an E-box binding site within this region that has been previously implicated in regulating IRS-2 in response to hormone stimulation inhibits hypoxic upregulation of IRS-2. We are currently investigating the factors that bind to this E-box to regulate IRS-2 expression. In addition, we have established that HIF is required for IRS-2 upregulation in hypoxic environments, and we are investigating if HIF acts in a direct or indirect manner to regulate IRS-2 expression. Identifying the mechanism by which IRS-2 expression is regulated by hypoxia is essential for developing novel methods to inhibit IRS-2 expression to suppress metastasis.
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 3291.
Abstract 3295: The type I insulin-like growth factor receptor (IGF1R) pathway driven metastasis signature correlates with poor prognosis and decreased distant metastasis-free survival in human breast cancer
Authors: Sachdev Deepali , Sarver Aaron 
Published: February 2011

Abstract
The insulin-like growth factors (IGFs) acting via the type I IGF receptor (IGF1R) regulate growth and metastasis of multiple types of cancers. Agents targeting IGF1R are currently being tested in phase II/III clinical trials. We have previously shown that IGF1R can regulate metastasis independently of primary tumor growth. In a model of high risk metastatic cancer using the MDA435/LCC6 metastatic cancer cells, we have shown that disruption of IGF signaling either with an antibody against IGF1R, AVE1642, or a dominant negative IGF-1R construct, does not affect growth in the mammary fat pad but inhibits pulmonary metastases and colonization of the lungs. Regulation of such a phenotype will not be measured in clinical trials and these findings imply that clinical trials of this therapeutic strategy may need to adjust their endpoints for assessing benefit by taking into account that inhibition of IGF1R signaling may inhibit metastasis but not primary tumor growth.
Here, we sought to develop an IGF1R driven metastasis signature that may be useful in selecting patients that could benefit from IGF1R targeted therapy and determine if changes in expression of the genes in the signature can be useful in monitoring response. Serum starved LCC6-WT cells (with wild-type functional IGF1R) and LCC6-DN (cells with dominant negative IGF1R) were treated with IGF-I, AVE1642 (antibody against IGF1R that inhibits metastasis but not tumor growth in the mammary fat pad), or AVE1642+ IGF-I for 4 and 24 hours and microarray analysis was performed using the U133 Plus 2.0 human arrays with 47,000 transcripts. Array data were analyzed to determine genes regulated by IGF1R signaling in these cells and if disruption of signaling with AVE1642 affected genes whose expression was regulated by IGF-I signaling. A total of 206 transcripts were regulated by IGF signaling in LCC6-WT cells and AVE1642 treatment reversed the effects of IGF1R signaling. 53 of the most significantly regulated genes were used to query two different human breast tumor datasets to determine if genes regulated by activation of IGF1R are associated with lymph node metastasis and poor prognosis in human tumors. IGF1R regulated metastasis signature genes were expressed in human tumors and were correlated to decreased survival and decreased distant metastasis free survival in breast cancer patients. Our results suggest that presence of IGF1R metastasis signature in patients confers prognostic value and identifying IGF1R driven metastasis signatures may be useful to identify and monitor patients who could benefit from IGF1R targeted therapy for inhibition of metastatic 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 3295.
Abstract 3296: Cell survival in colon cancer metastatic progression
Authors: Wang Wang , Brattain Michael G. 
Published: February 2011

Abstract
Colon cancer is the second most lethal malignancy in the United States. The majority of deaths are due to metastasis, for which no effective therapies are currently available. While much is known about oncogenic initiation of colon cancer, the mechanisms by which cancer cells survive and metastasize in spite of the cellular stresses associated with this process require further investigation. Resent studies indicated that deregulation of apoptosis contributes to metastasis and deregulation of Bcl-2 family members are correlated with cancer progression. We have initiated studies with a unique othotopic implant model based on closely related colon cancer cell lines. HCT116 and HCT116b cells were isolated from the same primary colon tumor. They both bear the H1047R PIK3CA mutation and form progressively growing invasive orthotopic primary tumors. However, only HCT116 cells exhibit robust metastatic potential. Interestingly, we found that Bcl-2 is highly expressed in HCT116 cells, but not in HCT116b cells. Overexpression of exogenous Bcl-2 in HCT116b cells enhanced their ability to withstand external stress, indicated by reduced levels of DNA fragmentation, reduced cytochrome c release from the mitochondria, and increased caspase activation. Immunoprecipitation assays revealed the formation of Bcl-2: Bax heterodimers, which has been shown to exert the anti-apoptotic property of Bcl-2. In complementary experiments, both shRNA-mediated stable knockdown and overexpression of dominant negative forms of Bcl-2 in metastatic HCT116 cells abolish its survival advantage against stress. These results indicate that modulation of Bcl-2 protein alone can reverse the sensitivity of HCT116 and HCT116b cells to stress-induced apoptosis. Current studies in our orthotopic model will determine whether alterations in Bcl-2 expression as well as complex formation of Bcl-2/Bax affect the metastatic potential of colon cancer in vivo, and consequently provide direct evidence as to whether cell survival control determines metastasis.
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 3296.
Abstract 3304: EAPII/TTRAP is overexpressed in HNSCC
Authors: Li Chunyang , Fan Songqing , Sun Shi-yong , Khuri Fadlo R. , Li Runzhao 
Published: February 2011

Abstract
EAPII/TTRAP, a novel protein we previously identified, was most recently recognized as the first enzyme that removes topoisomerase-mediated adducts at the 5′-phosphotyrosyl bond. EAPII/TTRAP restores 5′phosphate termini at double strand breaks preparing them for ligation. However, the physiological and pathological roles of EAPI I/TTRAP in human cells are elusive; in particular, it is unknown whether EAPII/TTRAP is involved in cancer. To determine the EAPII expression profile in the development of the Head and Neck Squamous Cell Carcinoma (HNSCC), we have developed a monoclonal antibody against EAPII suitable for immunohistochemistry (IHC). IHC was carried out in an HNSCC tissue array containing 34 cases of HNSCC and 12 peri-cancer or normal tissues. EAPII is not detectable in normal human oral squamous cells where HNSCC arises. With increased cell proliferation, weak staining of EAPII in the nucleus occurs. However, EAPII expression is significantly observed in HNSCC: Compared to 8% (1/12) in peri-cancer tissue, 82% (28/34) of HNSCC showed strong cytoplasmic-positive staining while nuclear staining reduced from 75% (9/12) to 35% (12/34). This result indicates that EAPII translocation to the cytoplasm might be an oncogenic factor that contributes to the progression of HNSCC. Consistent with the IHC study, high levels of EAPII expression are observed in many HNSCC cancer cell lines. Furthermore, lentivirus-delivered EAPII small hairpin RNA (shRNA) was employed to knockdown EAPII expression in HSNCC 686Ln-M4E cells. Cell growth curves were analyzed by SRB method. Lower cell growth was observed in the cells with reduced EAPII protein levels compared with cells infected with vector control or scramble shRNA.
Altogether, our data support the hypothesis that EAPII is a potential oncogenic factor and that the elevated level of EAPII may be involved in the HNSCC development. The identification of the role of EAPII in the HNSCC development using animal models will provide further insight into the biological significance of EAPII in cancer development and progression. This work was supported in part by National Cancer Institute award 5 P50 CA128613 SPORE in Head and Neck Cancer (SYS) and Startup Fund from the Department of Hematology and Medical Oncology (RL).
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 3304.
Abstract 3307: Cell-surface glycoproteomics identifies CUB-domain containing protein 1 to be associated with prostate cancer metastasis
Authors: Yang Lifang , Troyer Dean A. , Nyalwidhe Julius O. , Drake Richard R. , Semmes Oliver J. 
Published: February 2011

Abstract
Prostate cancer is still the most common and second leading cause of cancer death in men in the United States and is overwhelmingly lethal when metastatic. Evidence from histochemical analysis and experimental tumor models indicates alterations in cell-surface sialylation as a general observation associated with the metastatic potential of tumor cells. Our preliminary data from lectin staining also demonstrates changes of cell-surface sialylation in a syngeneic prostate cancer cell model, which includes two PC3 sublines, N2 (non-metastatic) and ML2 (highly metastatic). Characterization of cell-surface sialylated glycoproteins in this model system could provide new information related to the metastatic phenotype in prostate cancer. Thus, cell-surface sialoglycoproteins in the N2 and ML2 cell lines were metabolicly labeled with with an unnatural mannose analogue (AC4ManNAz); This was followed by chemoselective conjugation of the azido sugars with a biotinylated alkyne capture reagent via Cu (I) catalyzed click chemistry and affinity detection and enrichment by streptavidin-conjugated beads (or fluorescein). Captured glycoproteins were separated by 1D gel electrophoresis, in-gel proteolytic digestion, and protein identification by means of tandem mass spectrometry (LC-MS/MS). The expression of the targeted sialoglycoproteins was verified in our prostate cancer cell lines and clinical samples by means of Western blot, confocal microscopy and fluorescent immunohistochemistry. Forty three cell-surface N-linked glycoproteins were identified as differentially expressed between the PC3 metastasis variants, including CUB-domain containing protein 1 (CDCP1). Western blot analysis of the cell-surface glycoprotein enriched fractions and total cell lysate confirmed that CDCP1 was over-expressed in the metastatic ML2 cells. Expression of CDCP1 is dysregulated in prostate cancer tissues, with malignant glands showing a more intense cell surface staining pattern, whereas normal glands demonstrated weak membrane and intracellular granular staining on the basal side. We conclude that glycan metabolic labeling technology combined with mass spectrometry analysis provides a powerful tool for the identification of specific cell-surface glycoproteins that may contribute to prostate cancer metastasis, like CDCP1. Further studies are warranted to evaluate the clinical value of CDCP1 and to understand its function in prostate cancer progression.
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 3307.
Abstract 3309: Identifying glycoproteins in ER+ and ER- human breast cancer tissue samples
Authors: Semaan Suzan , Wang Xu Eddy , Emmett R. , Marshall Alan G. , Sang Qing-Xiang Amy 
Published: February 2011

Abstract
Breast cancer is the second leading cause of death from cancer in women. New biomarkers for cancer detection and treatment are needed to increase the life expectancy of breast cancer patients. Protein glycosylation is a post translational modification that gives a protein a new function. A change in the glycosylation on a glycoprotein often causes a change in function of that glycoprotein and such phenomenon has been correlated with cancerous transformation. Thus, glycoproteins in human breast cancer estrogen receptor positive (ER+) tissue and those in estrogen receptor negative (ER-) tissue, the more aggressive stage in breast cancer, are compared and a list of glycoproteins possibly showing a difference in their glycosylation were identified using double staining (glyco- and total protein staining) of the 2-DE gels followed by ESI-FTICR analysis and gel spot count was done using ImageQuant TL. Results show that 30% of the total lysate proteins are glycoproteins, where the total proteins in ER+ are slightly higher than that of the ER-, yet the difference between the glycoprotein in the ER+ and ER- is not significant. Alpha-1-acid glycoprotein, Alpha-1-antitrypsin glycoprotein, Annexin A1, Malate dehydrogenase mitochondrial precursor, Myosin-reactive immunoglobulin kappa chain variable region, IGKV1-5, Peroxiredoxin-1, and Superoxide dismutase mitochondrial precursor are the identified glycoproteins in both ER+ and ER- human breast tissue samples. Alpha-1-acid glycoprotein and Alpha-1-antitrypsin glycoprotein are mostly N-glycosylated proteins. Annexin A1, Malate dehydrogenase mitochondrial precursor, and Superoxide dismutase mitochondrial precursor are possibly N- or O-glycoslated proteins, while Myosin-reactive immunoglobulin kappa chain variable region, IGKV1-5, and Peroxiredoxin-1 are possibly mostly O-glycosylated proteins. Among those glycoproteins Alpha-1-acid glycoprotein, Alpha-1-antitrypsin glycoprotein, Annexin A1, Peroxiredoxin-1, Immunoglobulin gamma-1C region, and Superoxide dismutase mitochondrial precursor are important glycoproteins in breast cancer and possible biomarkers during the progression of human breast cancer. (This work was supported in part by grant BCTR0504465 from the Susan G. Komen for the Cure Breast Cancer Foundation, grants from the Florida Breast Cancer Coalition Research Foundation, the Elsa U. Pardee Foundation, and the Florida State University to Prof. Q.-X. Sang)
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 3309.
Abstract 3310: Ezrin is an independent prognostic factor in extremity soft tissue sarcomas
Authors: Carneiro Ana , Jönsson Mats , Rambech Eva , Rissler Per , Rydholm Anders , Nilbert Mef 
Published: February 2011

Abstract
Ezrin is a cytoskeleton protein actively involved in regulating the growth and metastatic capacity of cancer cells. It has recently been reported to be to be associated with poor prognosis high grade soft tissue sarcoma (STS) and to mediate growth and survival through AKT pathway.
To further validate the prognostic value of ezrin in STS, we evaluated 229 extremity primary STS using tissue microarrays and immunohistochemistry. Ezrin expression was correlated with metastasis during follow-up for at least 5 years or until death.185 of the 229 cases analyzed (80%) showed ezrin immunoreactivity in the membrane and cytoplasm of the tumor cells. Multivariate analysis with other known risk factors, including size, vascular invasion and necrosis showed that ezrin expression was significantly associated with development of distant metastasis during follow-up (P = 0.01, 95%CI 1.4-3.4). Ezrin expression was also correlated with AKT pathway changes, evaluated by gene expression.
Our findings suggest that ezrin is a promissing prognostic marker in highly malignant STS and support an interaction between ezrin and AKT in the genesis of STS metastasis.
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 3310.
Abstract 3311: Glycosylation alterations associated with pancreatic cancer EMT probed using gene expression in three model systems
Authors: Maupin Kevin , Sinha Arkadeep , Miller Jeremy , Ross Juli , Paulino Vincent , Keshamouni Venkat , Tran Nhan , Berens Michael , Webb Craig , Haab Brian B. 
Published: February 2011

Abstract
The lethal nature of pancreatic cancer is related to its propensity to disseminate at early stages and its resistance to chemotherapeutics. Cancer cells that have undergone epithelial-mesenchymal transition acquire these traits and may play an important role in pancreatic cancer progression. The identification of the defining molecular features and functional drivers of pancreatic cancer EMT may lead to new methods to control cancer progression. Particular glycosylation patterns are specifically associated with cellular differentiation and activation and play functional roles in cell migration and signal transduction. Therefore we hypothesized that pancreatic cancer EMT is characterized by specific glycosylation alterations that play functional roles in cancer cell differentiation or migration. As a first step toward investigating that hypothesis, we characterized the expression of glycan-related genes in three model systems of pancreatic cancer EMT. We used whole-genome microarrays to study gene expression in: 1) TGF-beta-induced EMT in two different cell lines; 2) a panel of 23 pancreatic cancer cell lines characterized as either epithelial-like or mesenchymal-like; and 3) actively-migrating and stationary cells from two different cell lines. We compiled a list of 585 genes involved in glycosylation (biosynthesis, sugar transport, glycan-binding, etc.) or EMT. Using this list, we found that each model system displayed both elevations and reductions with high significance in multiple glycan-related genes. The percentage of glycan-related genes showing changes exceeded the percentage of overall genes showing changes in each case, suggesting an important role of glycan alterations in EMT. To narrow the list of candidate genes for further study, we looked at the overlap in altered genes between the model systems. ST6GALNAC4, an enzyme that transfers sialic acid to particular presentations of the N-acetyl galactosamine monosaccharide, was elevated in the pancreatic cancer cell lines of all model systems. Glycan structures similar to those synthesized by ST6GALNAC4 are commonly associated with cancer. Genes involved in the sulfation and de-sulfation of glycosaminoglycans were frequently altered, as well as members of the mannose receptor family, each of which suggests routes of modulating extracellular interactions. These results support the involvement of glycan alterations in cancer EMT and suggest targets for the further study of mechanistic drivers of pancreatic cancer progression.
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 3311.