bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1032: Impact of HOXC9 recapitulation on cancer biology and clinical outcome in gastric cancer
Authors: Moon Sungmin , Hong Changsoo , Lee Sangrok , Zhao Xue-Feng , Lee Hyewon , Kim Semi , Han Sang-Uk , Chung Ik-Joo , Park Young-Kyu 
Published: February 2011

Abstract
The HOX genes encode transcription factors and may be implicated in the growth and the progression of many types of tumors. There are growing lines of evidence that dysregulation of HOX gene expression plays important roles in cancer. The aim of this study is to determine the level of HOXC9 expression during gastric cancer progression and the impact of its alteration on cancer biology and clinical outcome. HOXC9 expression was evaluated in normal mucosa, malignant legions, gastric cancer tissues by RT-PCR, western blot and immunohistochemistry. We established AGS gastric cancer cell in which HOXC9 was knock-down by shRNA and conditionally knock-down the HOXC9 expression by tetracycline-regulated gene expression (Tet-Off) system. The effect of HOXC9 knock-down on cell proliferation and apoptosis in AGS gastric cancer line were analyzed by tetrazolium salt-based proliferation assay (WST assay) and FACScan. Knockdown of HOXC9 by specific shRNA (67.3%) increased apoptosis, compared to scambled (7.3%) after 48 hours treatment of doxycycline, and increased active form of cellular apoptosis-related enzyme capsae-9, caspase-3 and poly (ADP-ribose) polymerase, whereas decreased expression of Bcl-xL, a mitochondria dependent anti-apoptosis factor. There was a gain or substantial increase of HOXC9 protein expression according to gastric cancer progression. Kaplan-Meier survival curves showed that HOXC9 overexpression is correlated with inferior disease-specific survival (P&lt;0.001). multivariate Cox repression analysis revealed HOXC9 expression was an independent poor prognostic factor (Hazard ratio, 1.74; 95% CI, 1.01 to 2.99; P=0.047). We then demonstrated that HOXC9 directly regulated Bcl-xL transcription by binding to a HOXC9-responsive element in the Bcl-xL promoter by reporter gene assay, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA). In conclusion, these results suggest that HOXC9 overexpressed in advanced gastric cancer setting and its expression should be useful as a prognostic marker in gastric cancer patients. HOXC9 dependent Bcl-xL overexpresion may be an important mechanism by which HOXC9 protects gastric cancer cells from apoptosis.
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 1032.
Abstract 1035: Bcl2 is regulated by PKC and Akt and is associated with resistance to cisplatin in endometrial cancer cells.
Authors: Rouette Alexandre , Girouard Julie , Leblanc Valérie , Parent Sophie , Asselin Éric 
Published: February 2011

Abstract
Endometrial carcinomas often show resistance to cisplatin. Bcl2 has been shown to be associated with cisplatin resistance in different types of cancers. However, there is no information concerning its possible involvement in chemoresistance and its regulation in endometrial carcinomas. We have tested the ability of cisplatin to induce apoptosis in KLE, a resistant endometrial carcinoma cell line, and examined the putative role for Bcl2 in regulating drug sensitivity. We have investigated the impact of cisplatin treatment on Bcl2 family members and Xiap, an inhibitor of caspase activity. Cisplatin treatment upregulated Bcl2 protein expression in a time-dependant manner in KLE cells, but had no significant impact on the levels of Bax, Bcl-xL and Xiap proteins. As demonstrated by RT-PCR, Bcl2 mRNA was not upregulated in response to cisplatin, suggesting that cisplatin act on Bcl2 expression through a post-translational mechanism. In KLE cells, Bcl2 inhibition by HA14-1 led to increased apoptosis induced by cisplatin. It has been shown that Akt, MAPK and PKC pathways are involved in the regulation of Bcl2 under various conditions and in different cell types. Therefore, KLE cells were treated with inhibitors of MAPK (PD98059) and PKC (CalphostinC) prior to cisplatin treatment. Inhibition of PKC prevented cisplatin-dependant upregulation of Bcl2 protein, while MAPK inhibition had no impact. We previously showed that KLE cell line express high levels of phosphorylated Akt (pAkt) isoforms. Then, KLE cells stably expressing shRNA for all three Akt isoforms were established. Treatment of these cells with cisplatin prevented the increase of Bcl2 expression and led to increased apoptosis by cisplatin. These data suggest a role for Bcl2 in cisplatin resistance in endometrial carcinoma cells. Also, they indicate that PKC and Akt are involved in regulation of Bcl2 expression in this experimental model.
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 1035.
Abstract 1037: Lysophosphatidic acid upregulates Bcl-2 production and secretion in ovarian cancer cells
Authors: Anderson Nicole S. , Rojiani Mumtaz , Kruk Patricia A. 
Published: February 2011

Abstract
Lysophosphatidic acid (LPA) is elevated in the plasma and ascites fluid of ovarian cancer (OC) patients and has been proposed as a diagnostic tool for OC. LPA is the simplest glycerophospholipid and has been shown to have an extensive range of biological activities. LPA is involved in wound healing and tissue regeneration, cell proliferation and survival, platelet aggregation, and tumor cell invasion. In addition, LPA elicits anti-apoptotic activity through upregulation of Bcl-2 in other systems. Bcl-2, the prototypical anti-apoptotic protein, is commonly overexpressed in OC. The purpose of this study was to determine whether LPA regulates Bcl-2 in OC. Using an in vitro cell culture model system, OC cells were treated ± LPA. We found that LPA increased Bcl-2 expression at the protein and message levels using western immunoblotting, ELISA and luciferase reporter assays. Interestingly, LPA also promoted Bcl-2 secretion by OC cells, which is a novel action of Bcl-2. Secreted Bcl-2 appears to modulate angiogenesis by affecting endothelial cell migration as well as tube formation in an in vitro angiogenesis assay using HUVECs. Given that both LPA and Bcl-2 are potential targets in ovarian cancer intervention, elucidating their inter- and regulatory relationships may be of clinical importance and warrants further investigation.
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 1037.
Abstract 1051: Quantitative assay for simultaneous assessment of phosphorylation and cell migration
Authors: Olive Michael , Chen Huaxian 
Published: February 2011

Abstract
Introduction: Cell migration is a critical process in angiogenesis and inflammation as well as tumor progression and metastasis. The acquisition of the ability to migrate is dependent on the activation of key cell signaling pathways, two of which are modulated by AKT and ERK kinases. Screening assays that can simultaneously quantify cell migration and the activity of the underlying signaling kinases may facilitate more efficient identification of therapeutic compounds.
Methods: Oris™ Cell Migration Assay plates (Platypus Technologies, Madison, WI) were seeded with HT1080 cells. The Oris plates contain a stopper, which when removed following 24 h cell growth, creates a defined cell-free region on the plate. After removal of the stoppers, PI3 kinase and MEK inhibitors were added and cells allowed to migrate. After fixing and permeabilization, cell migration was measured by staining with primary mouse antibodies against total ERK2 and histone H3, application of a plate-specific mask that allowed detection of only migratory cells, and quantification by staining with IRDye 680-labeled goat anti-mouse antibodies. Phosphorylation was measured simultaneously by staining with rabbit antibodies against either phospho-AKT or phospho-ERK and detection with IRDye 800CW-labeled goat anti-rabbit antibodies. Fluorescence was detected by scanning with either an Aerius or Odyssey instrument.
Results: AKT and ERK phosphorylation were specifically inhibited by their respective drugs. The level of inhibition of phosphorylation correlated with decreased migration in a dose-dependent manner. The robustness of the assay was exemplified by its high signal to noise ratio.
Conclusions: Anti-cancer drugs developed by assessment phosphorylation state alone may identify hits that inhibit the target kinase, yet fail to retard functional outcomes such as migration and proliferation. We have designed a quantitative assay that allows for simultaneous assessment of a biochemical characteristic, namely phosphorylation state, and a functional parameter related to metastasis. This quantitative assay may facilitate a better understanding of the mechanisms underlying cell movement and metastasis, and may facilitate a more efficient means of developing anti-cancer drugs.
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 1051.
Abstract 1055: Character of tumor assocated protien recognized by monoclonal antibody against yunnan gejiu lung cancer
Authors: Wang Qinqin 
Published: February 2011

Abstract
Character of tumor assocated protien recognized by monoclonal antibody against Yunnan Gejiu lung cancer: about protein N35
WANG Qinqin
The Clinical Reseach Center. The First Hospital of Kunming Medial College
Kunming, Yunnan, P.R. China 650032
ABSTRACT Objectives: To identify and characterize lung cancer associated protein N35 and attempt to learn the prospective possibility of the clinical application of the protein N35. Methods: Immunoprecipitation, immunoblotting, differential centrifigation and subcellular assay, immunohistochemistry, Nglycanase digestion, mitotic cell immunoflourescence and multiple methods of affinity chromatography have been used with the monoclonal antibody N-35 to detect the distribution of the protein N35 among the various cancer cell lines and normal human tissue, the relationship between the protein N35 and glycoprotein, the location of the subcellular structure and chromosomal domain of the protein N35,the most effective way of purification of tumor associated protein N35. Results: The protein N35 is a glycoprotein, distributes to the human lung cancer cell line GLC-82, human cervical cancer cell line Hela, human hepatic cancer cell line HepG-2 and human breast cancer cell line PMC with different relative molecular mass(Mr), but no expression of the protein ingredient in normal human fresh tissue; concentrates at the nuclei significantly, much more than at the mitochondrail and membrane, locates at the centriole of the chromosomal domain. Conclusions: The lung cancer associated protein N35 might be expressed only by the cancer cells and related with the proliferation of cancer cells as a role of tumor cell growth regulator.
Keywords: Lung cancer cells, Tumor associated protein, Glycoprotein, Centriole
Qinqin Wang
Prof of The Clinical Reseach Center. The First Hospital of Kunming Medial College
295 Xichang Rd. 650032
Kunming Yunnan, P.R. China
Tel:868714191985
Fax: 868715336015
Email: zys@public.km.yn.cn
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 1055.
Abstract 1062: Numb, an intrinsic Notch inhibitor, possesses a tumor suppressor role through regulation of Plk1 localization during mitosis
Authors: Schmit Travis L. , Setaluri Vijayasaradhi , Spiegelman Vladimir S. , Ahmad Nihal 
Published: February 2011

Abstract
Numb, an intrinsic Notch inhibitor and cell fate determinant, has been shown to possess many functions in proper cell division. These include its role in endocytosis, a tumor suppressor role via regulation of p53 stability, and asymmetric self renewal during progenitor cell division. Studies have shown that a proper localization of fully functional Plk1 is required for mitotic entry, progression and exit. Plk1 has been shown to play a critical role in bi-polar spindle formation and maturation during mitosis. It has been shown that chemical inhibition as well as genetic knockdown of Plk1 results in cells forming a mono-polar spindle phenotype surrounded by DNA rather than a bi-polar arrangement on either side of the metaphase plate. This severe mitotic phenotype results in a G2/M cell cycle arrest and mitotic catastrophe. Also, milder inhibition of Plk1 has been shown to result in errors in bi-polar spindle formation including multi-polar phenotypes or incomplete microtubule attachment and division. Some of these less pronounced phenotypes may not prevent cell division and may contribute to cellular aneuploidy and cancer. In this study, employing melanoma cell lines A375 and HS294T, we demonstrated that Numb and Plk1 interact as shown by co-immunoprecipitation and immunofluorescent assays. In addition, we found that both Plk1 and Numb co-localize to the spindle poles in metaphase. Further, using lentiviral shRNA knockdown of Plk1 or Numb, we also found that loss of Plk1 or Numb dysregulates the localization of the other. Most striking was the pronounced mislocalization of Plk1 from the spindle poles. Although, the majority of metaphase cells were still bi-polar, there was a marked increase in mislocalized γ-tubulin in some instances. Additionally, in the cells with two defined spindle poles, γ-tubulin still appears to be less pronounced at strictly the spindle pole with an apparent indistinct staining surrounding the poles indicating that Numb may not be directly required for γ-tubulin localization to the spindles but the misregulated Plk1 localization slows or prevents spindle pole maturation and γ-tubulin recruitment. Conversely, the differing phenotypes of γ-tubulin localization may also be explained by a redundant role of Numb-like, though this is yet to be explored. Overall, these data suggested that Numb may possess tumor suppressor functions by regulating proper Plk1 localization and proper spindle pole maturation.
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 1062.
Abstract 1068: Cooperation between BRCA1 and Aurora A kinase regulates in vitro crisis in epithelial cells derived from benign ovarian tumors
Authors: Marion Christine M. , Dubeau Louis , Yu Vanessa 
Published: February 2011

Abstract
Aneuploidy, as defined by a chromosome number that is not a multiple of the haploid number, is a hallmark of cancer. We used an in vitro cell culture model where explants of benign epithelial ovarian tumors (cystadenomas) were transfected with an expression vector for SV40 Large T Antigen, allowing bypass of senescence due, in part, to p53 and Rb inhibition by this antigen. We previously showed that such cells eventually reach a crisis event that is associated with a cell cycle arrest at the M phase and is independent of telomere attrition. Cells that recover from this event do not complete cytokinesis and become polyploid, which is a precursor to aneuploidy. Decreased BRCA1 expression facilitates abrogation of mitotic arrest, leading to increased rates of aneuploidy.
We hypothesized that Aurora A plays a role in regulating this ploidy-associated crisis event by acting as an upstream regulator of BRCA1 expression. Here we show that Aurora A kinase activity and expression is up-regulated in cells approaching crisis. Over-expression of Aurora A resulted in decreased levels of BRCA1, resulting in increased tetraploidy and aneuploidy, secondary to cells overcoming a ploidy-associated crisis. Levels of BRCA1 expression increased upon knockdown of Aurora A kinase using siRNA, further suggesting an inverse relationship between expression levels of these two proteins. Inhibition of Aurora A in cultured ovarian cystadenomas approaching crisis led to decreased cell proliferation and a concomitant decrease in tetraploidy. We tested the hypothesis that this was associated with an increase in crisis-related apoptosis by knocking down Aurora A kinase using siRNA technologies in cells approaching crisis, followed by western blotting using antibodies against PARP and cleaved CASPASE 7 fragment. The results indeed showed increased levels of these two protein fragments upon Aurora A knockdown, indicating activation of a caspase-regulated apoptotic pathway.
Our findings suggest a novel role for Aurora A's influence on BRCA1 expression levels in cells approaching ploidy dependent crisis. This may, in part, explain the increased rate of near polyploidy associated with high grade ovarian carcinomas and may provide insights into the mechanism underlying aneuploidy development in epithelial cancers in general.
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 1068.
Abstract 1071: DeltaEF1 promotes breast cancer cell proliferation through down-regulating p21 expression
Authors: Hu Fen , Wang Chuan , Zhu Tianhui , Yang Shuang 
Published: February 2011

Abstract
Background: Deregulation of the cell cycle and abnormal cell proliferation are involved in breast carcinogenesis. Recent evidence suggests that deltaEF1, a zinc finger-homeodomain transcription factor, is a potential regulatory factor at the crossroad between proliferation and differentiation. However, how deltaEF1 mediates its proliferative effects in tumorigenesis has not been recognized yet.
Materials and Methods: Quantitative RT-PCR and immunoblotting were used to determine the expressions of deltaEF1, p21, p27, CDK2, CDK4, and CDK6 at the mRNA and the protein levels, respectively, in MCF-7, MDA-MB-231, T47D, and ZR-75-1 breast cancer cells, as well as in 22 breast cancer specimens. Cell proliferation and BrdU incorporation assays as well as flow cytometry were used to determine cell proliferation of MDA-MB-231 cells with deltaEF1-overexpression or deltaEF1 siRNA knockdown. Luciferase assay was used to determine deltaEF1-driven transcriptional activities of the wild-type and mutant human p21 promoters. Quantitative CHIP assay was used to detect the direct association of deltaEF1 with the wild-type human p21 proximal promoter.
Results: We found that ectopic expression of deltaEF1 in MDA-MB-231 cells significantly promoted cell proliferation as indicated by an increase of cells in S phase of the cell cycle. As anticipated, deltaEF1 knockdown by RNA interference decreased the cells in S phase, suggesting a role of deltaEF1 in the G1-S transition of breast cancer cells. Importantly, we also demonstrated that deltaEF1 down-regulated p21 with up-regulation of CDK2 and CDK4. Furthermore, our studies revealed that deltaEF1 inhibited p21 transcription after recruited to the E2-box element on the p21 promoter. Depletion of endogenous deltaEF1 was sufficient to trigger p21 expression in MDA-MB-231 cells, resulting in the cell cycle arrest. In addition, an inverse correlation of deltaEF1 and p21 expression was detected in both breast cancer cell lines and clinical tumor specimens, further supporting the role of p21 down-regulation in the stimulatory effect of deltaEF1 on cell proliferation.
Conclusions: We conclude that deltaEF1 plays a critical role in promoting cell proliferation in breast cancer. Given that higher expression level of deltaEF1 is associated with more progressive phenotype of breast cancer, our collective data suggest that deltaEF1 is a key regulatory factor at the crossroad between proliferation and differentiation, thus underscoring tumor progression and 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 1071.
Abstract 1079: Targeted disruption of Nemo-like kinase inhibits tumor cell growth by simultaneous suppression of cyclin D1 and CDK2 in human hepatocellular carcinoma
Authors: Jung Kwang Hwa , Kim eong Kyu , Noh Ji Hein , Eun Jung Woo , Bae Hyun JIn , Xie Hong Jian , Park Wong Sang , Lee Jung Young , Nam Suk Woo 
Published: February 2011

Abstract
The wnt/β-catenin signaling pathway regulates various aspects of development and plays important role in human carcinogenesis. Nemo-like kinase (NLK), which is mediator of wnt/β-catenin signaling pathway, phosphorylates T-cell factor/lymphoid enhancer factor (TCF/LEF) factor and inhibits interaction of β-catenin/TCF complex. Although, NLK is known to be a tumor suppressor in wnt/β-catenin signaling pathway of colon cancer, the other events occurring downstream of NLK pathways in other types of cancer remain unclear. In the present study, we identified that expression of NLK was significantly up-regulated in the HCCs compared to corresponding normal tissues in five selected tissue samples. Immunhistochemical analysis showed significant over-expression of NLK in the HCCs. Targeted-disruption of NLK suppressed cell growth and arrested cell-cycle transition. Suppression of NLK elicited anti-mitogenic properties of the Hep3B cells by simultaneous inhibition of cyclinD1 and CDK2. The results of this study suggest that NLK is aberrantly regulated in HCC, which might contribute to the mitogenic potential of tumor cells during the initiation and progression of hepatocellular carcinoma; this process appears to involve the induction of CDK2 and cyclin D1 and might provide a novel target for therapeutic intervention in patients with liver 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 1079.