bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2297: Transcriptome profiling of invasion phenotype associated with epithelial-mesenchymal transition in esophageal cancer
Authors: Li Hsiao-Fang , Peng Talun , Cheng Ann-Joy 
Published: February 2011

Abstract
The esophageal cancer (ESC) is one of the ten-leading cancers in Taiwan with highly metastatic potential. The aim of this study was to clarify relevant alterations of gene expression associated with the invasive phenotype of ESC. To reduce heterogeneity and to obtain data on genes specifically involved in invasive mechanism, we established a highly invasive ESC subline (CE48) through 10 passages of in vitro Matrigel selections. This subline exhibited increases of invasion and migration abilities with the ascending generations, in accompany of morphological alteration from epithelial type to mesenchymal type, suggesting an epithelial- mesenchymal transition (EMT) was occurred during this Matrigel selection. In support of this finding, five molecular EMT markers were also changed accordingly. Affymetrix cDNA microarray was used to compare the transcriptomes between the parental and the EMT-associated invasion subline. Heretical cluster and algorithmic analyses of the microarray dataset revealed that several functional pathways associated with these phenotypic alterations. On the other hand, 10 genes were examined for the potential differential expressions between parental and invasion subline by RT-PCR or western blot analysis. In which, TKT, FLNA, FN1, Gp96, Slug and IQGAP1 were found over-expressed in the invasion subline, suggesting a positive association in the regulation of EMT-associated invasion. Knockdown of TKT by siRNA further demonstrated suppression of cell invasion. Therefore, the EMT-associated invasion sublin and transcriptome profiling of the cells were determined. Results of this study provide molecular knowledge in the EMT-associated metastasis in ESC.
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 2297.
Abstract 2298: BP1 upregulates Twist, a trigger of EMT and cancer metastasis
Authors: Berg Patricia E. , Hwang Bin-Jin , Rheey Jinguen 
Published: February 2011

Abstract
BP1 Upregulates Twist, a Trigger of EMT and Cancer Metastasis
Bin-Jin Hwang, Jinguen Rheey, and Patricia E. Berg
George Washington University, Department of Biochemistry and Molecular Biology,
Washington, D.C.
Background. We have cloned a gene, BP1, which is a member of the homeobox gene family of transcription factors. Increasing evidence suggests that homeobox genes are important in malignant transformation and tumorigenesis, and our recent studies have shown that BP1 may play a role in breast cancer cell survival, aggressiveness and metastasis. BP1 protein (pBP1) is expressed in 80% of invasive ductal breast tumors, and is associated with breast cancer aggressiveness: 100% of estrogen receptor negative tumors and 89% of the tumors of African American women are BP1 positive. Now we have evidence that BP1 may regulate the epithelial to mesenchymal transition (EMT). EMT, a process in which cancer cells lose their epithelial features and gain mesenchymal markers, enables tumor cells to become more invasive and migratory, and can lead to metastasis. BP1 upregulates Twist, a basic helix-loop-helix (bHLH) transcription factor which triggers EMT. Our objective is to determine whether BP1 plays a role in induction of EMT. Materials and Methods. The expression levels of Twist, E-cadherin and vimentin were observed on microarrays after probing with RNA from MCF-7 cell lines overexpressing BP1. RNA levels were verified by real-time PCR and protein levels by Western blotting and, in some cases, by confocal microscopy. Summary. Twist mRNA expression on microarrays is higher in MCF-7 cells overexpressing BP1 compared with cells containing an empty vector. Real-time PCR confirmed that Twist mRNA is increased five-fold in cells with high levels of BP1, and Western blots demonstrated that Twist protein is also elevated in the same cells. We have discovered a potential DNA binding site for pBP1 in the Twist promoter, suggesting that BP1 may directly regulate Twist. This will be verified by ChIP. Expression of two genes regulated by Twist was also examined: Twist activates vimentin and represses E-cadherin. Cells overexpressing pBP1 also show increased vimentin and decreased E-cadherin. The effect of increased pBP1 on cell migration is under investigation. Conclusions: BP1 stimulates Twist expression in MCF-7 breast cancer cells, resulting in increased vimentin and decreased E-cadherin levels. We therefore hypothesize that BP1 is upstream of Twist and induces EMT. If BP1 is required for EMT, it may be a good target for therapy of metastatic tumors.
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 2298.
Abstract 2301: Cross-species expression profiling identifies novel genes differentially modulating epithelial-mesenchymal transition program and cell migration/invasion capability
Authors: Zhang Haijun , Wu Sherwin , Wu Feng , Ethier Stephen P. , Miller Fred , Wu Guojun 
Published: February 2011

Abstract
Despite remarkable advances in research and clinical management, metastatic breast cancer remains incurable and causes most deaths in human breast cancer patients due to the unavailability of specific, targeted therapy. Therefore, identification of functional metastasis genes and further unveiling the molecular mechanisms underlying metastasis process remains the top priority in cancer research field. In recent years, much evidence supports the notion that epithelial-mesenchymal transition (EMT), a developmental program involved in a variety of tissue remodeling events, contributes to cancer cell plasticity and to the invasive potential of transformed epithelial cells. However, the legitimacy of EMT is still challenged by disagreements among pathologists who dismiss EMT as a fallacy.
Utilizing a cross-species expression profiling strategy which combined microarray technique and model cell lines, we identified 22 up-regulated and 12 down-regulated genes as an essential genetic program in both human and mouse highly-metastatic model cell lines. About half of the gene candidates are novel and their roles in metastasis have not been reported. We randomly selected four genes and investigated their roles in metastatic characteristics including EMT program and cell migration and invasion. Overexpression of GCNT2 gene (an up-regulated gene candidate) not only led to a marked increase of cell migration and invasion, but also led to marked alterations in epithelial-mesenchymal transition (EMT) program. Ectopic expression of MAPK12 (another upregulated gene) only changed the EMT program but has no effect on cell migration and invasion. Overexpression of IRX5 (a down-regulated gene) not only led to a marked decrease of cell migration and invasion in vitro, but also a modulation of EMT program. However, expression of PHLDA3 (another down-regulated gene) only affect the cell migration and invasion, but has no effect on EMT program. These results highlight the feasibility of the cross-species expression profiling approach as a strategy to identify gene targets that are involved in breast cancer metastasis. The results of the functional studies for randomly selected genes further suggest that this multigenic program is consisted of different genes that play various roles in controlling EMT and/or Cell migration and invasion ability. Further studies are needed to investigate the effect of these novel gene candidates on metastasis in vivo and as therapeutic targets for treatment of breast cancer 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 2301.
Abstract 2306: The prognostic impact of epithelial mesenchymal transition markers in primary diffuse gastric carcinoma and their relative lymph nodes
Authors: Malouf Gabriel G. , Tomasic Gorana , Marty Virginie , Malka David , Vielh Philippe , Ducreux Michel , Boige Valerie 
Published: February 2011

Abstract
Background: The accumulating evidences for epithelial mesenchymal transition (EMT) are important in experiments conducted in cell culture and rodents. However, pathologists still debate the existence of EMT and its impact on cancer progression. The purpose of this present study was to investigate the distribution of EMT biomarkers in primary diffuse gastric carcinoma (DGC) and their relative lymph nodes (LN) and to correlate them with clinical outcome.
Patients and methods: The study included 51 consecutive patients who underwent surgical resection in our institution between January 1991 and December 2007 for DGC. A tissue-microarray was constructed using paraffin-embedded tissues from gastrectomy (n=51) and matched LN (n=37). Expression of c-MET, E-cadherin, cytokeratin and vimentin were assessed by immunohistochemistry (IHC) in primary DGC, their relative LN and non-tumoral adjacent tissues.
Results: Membranous c-Met overexpression was found in 32% of primary DGC and 38% of LN. Membranous E-cadherin expression was found in 70% of both primary CDG and LN. All tumors expressed cytokeratin and there was no expression for vimentin neither in primary DGC nor in their relative LN. Although there was a high correlation in E-cadherin expression between primary DGC and their relative LN (r2 = 0.93), a poor correlation for c-MET expression (r2 = 0.02) was found. Univariate analysis for recurrence-free survival (RFS) and overall survival (OS) were performed for the following parameters: TNM stage, c-MET and E-cadherin expression both in primary DGC and their matched LN. LN overexpression of c-MET was the only prognostic factor for better relapse-free survival (RFS) (HR= 2.82, CI95%:1.27-6.85) and overall survival (OS) (HR= 2.41, CI95%:1.05-5.52) for the entire cohort.
Conclusions: Our findings indicated that c-MET overexpression did not correlate between primary DGC and their relative LN and that only LN c-MET overexpression had a prognostic impact. Conversely, there was a high correlation between E-cadherin, vimentin, and cytokeratin expression between the primary DGC and their relative LN.
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 2306.
Abstract 231: Mechanism of bone metastasis in prostate cancer: Role of anterior gradient homolog 2
Authors: Chanda Diptiman , Sawant Anandi , Isayeva Tatyana , Ponnazhagan Selvarangan 
Published: February 2011

Abstract
Prostate cancer commonly metastasizes to the skeleton in advanced stages and leads to significant decline in life expectancy. In a recent study we demonstrated enhanced proliferation of the human prostate cancer cell line PC3 when cultured in the presence of bone marrow conditioned medium (BMCM). In order to identify key molecules involved in increasing proliferation rate, total RNA was isolated from PC3 cells grown in either BMCM or regular medium and subjected to cDNA microarray analysis. Results indicated a significant up-regulation of anterior gradient homolog 2 (AGR2) in the PC3 cells cultured in BMCM compared to those grown in regular medium. AGR2 is a secreted protein and originally reported for its involvement in the formation of forebrain and mucus-secreting cement gland in the frog Xenopus laevis. AGR2 is also highly expressed in human adenocarcinomas of the prostate, breast, esophagus and the pancreas and a study indicated poor survival of prostate cancer patients with higher AGR2 expression. We compared AGR2 gene expression by RT-PCR in different metastatic prostate cancer cell lines, isolated from the bone (PC3 and C4-2B), brain (Du145) and the lymph node (LnCap). Highest AGR2 expression was observed in bone metastatic cell lines, mainly PC3 cells and least expression was observed in Du145 cells. PC3 cells expressing firefly luciferase were also injected via intra-cardiac route into 6 week-old SCID mice and widespread metastases were observed in the lung, heart, adrenal and bone. Three weeks after the inoculation of the PC3 cells, the mice were sacrificed, tumor cells were harvested from various metastatic sites, total RNA isolated and subjected to RT-PCR analysis for AGR2 expression. Interestingly, highest AGR2 expression was observed in PC3 cells isolated from bone microenvironment, suggesting that AGR2 may have a potential role in prostate cancer bone metastasis. To test this hypothesis, we developed a subclone of PC3 cells with targeted knock down of AGR2 transcripts using lentivirus shRNA vector and tested the cell clone in vitro by implanting intra-tibially or subcutaneously in SCID mice. Results of this study indicated a failure of tumor development in AGR2 knocked down PC3 clones.
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 231.
Abstract 2310: Snail-induced epigenetic regulation and its implication in plasticity of cellular morphology
Authors: Lin Tong , Ponn Alison , Lu Jianrong 
Published: February 2011

Abstract
Epithelial and mesenchymal cells exhibit distinct phenotypic and functional characteristics, yet the two cell types possess substantial plasticity and are interconvertable. Bidirectional transitions between epithelial and mesenchymal cells play crucial roles in physiological and pathological processes. Both epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are fundamental to embryonic development. In human cancer, EMT confers migratory and invasive properties on carcinoma cells, thereby promoting tumor invasion and dissemination. Moreover, EMT may endow cells with stem cell-like traits. After migrating tumor cells reach ectopic organ sites, conversion of mesenchymal tumor cells to epithelial cells through MET (including differentiation of tumor stem cells) may facilitate macrometastatic growth. However, despite its critical relevance in normal development and cancer metastasis, the molecular basis underpinning the interconvertibility between epithelial and mesenchymal states remains incompletely understood.
The zinc-finger transcription factor Snail induces EMT by directly repressing E-cadherin, a defining marker of epithelial cells. Here we show that Snail physically interacts with and recruits the histone demethylase LSD1 to the E-cadherin promoter to remove dimethylation of lysine 4 on histone H3 (H3K4m2), a histone modification associated with active chromatin. Furthermore, demethylation of H3K4m2 by LSD1 is essential for Snail-mediated transcriptional repression. In contrast to H3K4me2, the active trimethylated H3K4 (H3K4m3) mark is not a substrate for LSD1 and it remains at high levels at the inactive E-cadherin promoter despite Snail expression. In addition, Snail induces H3K27 trimethylation (H3K27m3), a repressive chromatin mark. As a consequence, the Snail-repressed E-cadherin promoter simultaneously possesses opposite H3K4m3 and H3K27m3 marks, a pattern characteristic of bivalent chromatin modifications. Bivalent chromatin domains were initially identified and are enriched in stem cells. Bivalent promoters are inactive but are poised for activation. Although it awaits to be determined whether Snail-induced chromatin bivalency might contribute to cellular stemness, this observation suggests that the E-cadherin gene repressed by Snail remains in a transcriptionally ready state for re-activation, which may be critical for MET. These results exemplify how a bivalent chromatin state is established and provide new insights into epigenetic regulation of E-cadherin transcription and the plasticity of cellular morphology.
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 2310.
Abstract 2317: Oct4 impacts migration of breast cancer via Epithelial-to-mesenchymal transition related manner
Authors: Hu Jiajia , Guo Quanjun , Li Na , Xiang Rong , Tan Xiaoyue 
Published: February 2011

Abstract
Recent studys suggest that Oct4, a key regulator in maintenance of the embryonic stem cell pluripotency and proliferation, is relevant with the malignant characteristic of breast cancer. This study aims to investigate the role of OCT4 in the mechanism underlying the migration of breast cancer. We compared Oct4 expression in cultured MCF-7 and MDA-MB-231 cell, both of them are original from breast dust epithelial cell while the migration capacity of MDA-MB-231 cell is strikingly higher than that of MCF-7 cell. Result of western blot showed that expression level of Oct4 in MCF-7 cell was much higher than that in MDA-MB-231 cell. Then, we abolished Oct4 expression MCF-7 cell using siRNA technology. Trans-well assay result showed Oct4 down-regulation significantly increased the number of migrated cells. The expressions of E-cadherin andα-SMA, accepted epithelial and mesenchymal marker separately, were examined by western blot method. Upon down-regulation of Oct4, E-cadherin expression was inhibited whileα-SMA expression was significantly up-regulated. Real-time PCR result showed Fibronetin mRNA expression was also significantly up-regulated after Oct4 down-regulation. Further, we added TGF-β1 to cultured MCF-7 cell and then examined Oct4, E-cadherin and α-SMA expression level with Western blot. The results showed that TGF-β1 significantly inhibited E-cadherin while induced α-SMA expression in both time- and dose-dependent manner. At the same time, Oct4 expression was also highly down-regulated with the treatment of TGF-β1. Interestingly, Snail expression, which is a critical transcription factor in epithelium to mesenchymal transition (EMT) program, is significantly increased with the down-regulation of Oct-4 expression. Our study seemed to implicate transcription factor OCT4 in migration of breast cancer via EMT-related manner and this effect is likely associated with the impact of Oct-4 on the expression of Snail.
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 2317.
Abstract 232: PAX3-FOXO1a target genes in alveolar rhabdomyosarcoma: Possible therapeutic targets
Authors: Marshall Amy D. , van der Ent Martijn A. , Grosveld Gerard C. 
Published: February 2011

Abstract
Rhabdomyosarcoma (RMS) is a pediatric soft tissue tumor that is derived from skeletal muscle and expresses many muscle specific proteins. Most commonly RMS presents in one of two histological subtypes; Embryonal RMS (ERMS) or Alveolar RMS (ARMS). The ARMS subtype is more aggressive, more prone to metastasis and has the poorest prognosis. Over 75% of ARMS tumors possess a t(2;13)(q35;q14), or the variant t(1;13)(p36;q14) chromosomal translocation which generates a PAX3-FOXO1a or PAX7-FOXO1a fusion protein, respectively. Using murine primary myoblasts (a likely cell of origin for rhabdomyosarcoma), PAX3 and PAX3-FKHR were ectopically expressed and microarray analysis was performed to identify differentially regulated genes. Several genes were identified and two genes, Cannabinoid Receptor 1 (Cnr1/Cb1) and the pro-apoptotic BH3-only protein Noxa (Pmaip1), were chosen for further study.
In primary myoblasts, Cnr1 is required but not sufficient to enhance the invasive capacity of PAX3-FOXO1a expressing primary myoblasts. This appears to be mediated through Cnr1 constitutive activity. In vivo the Cnr1 inverse agonist AM251 prevents lung metastasis formation in immunocompromized mice. This implicates Cnr1 as a potential therapeutic target to inhibit the metastatic capacity of ARMS tumors.
Noxa expression is increased in PAX3-FOXO1a expressing primary myoblasts in a p53-independent manner. Moreover, PAX3-FOXO1a expression, through the up regulation of Noxa, increases the sensitivity of primary myoblasts to bortezomib and GSI-1, which also induce apoptosis in a p53-independent, Noxa-dependent manner. In addition, the up regulation of Noxa increases cell sensitivity to the anti-apoptotic Bcl-2 family inhibitor ABT-737. Bortezomib treatment in vivo significantly inhibits the growth of subcutaneous ARMS model tumors and prolongs the survival of treated animals.
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 232.
Abstract 2321: Expression of functional forms of αvβ3 and αvβ5 integrins, laminin-5 and vitronectin in common human tumors: Consequences for cilengitide targeting
Authors: Sipos Bence , Henopp Tobias , Kalthoff Holger , Klöppel Günter , Goodman Simon L. 
Published: February 2011

Abstract
Interactions between integrins and the extracellular matrix are believed to play an important role in tumor cell survival, division and metastasis, and in tumor angiogenesis. We studied the expression of integrins αvβ3 and αvβ5, and their key ligands in the extracellular matrix in freshly frozen sections of human colorectal, breast, lung and ovarian tumors. We applied immunohistochemistry using anti-integrin monoclonal antibodies specific for functional heterodimeric forms. Prominent expression of αvβ3 was strongly associated with tumor-related vessels (20/21 colorectal, 31/33 lung, 19/19 breast and 7/10 ovarian) but also in other stromal (fibroblastic) cells in &gt;80% of the cases. αvβ5 was almost uniformly detectable in tumor stroma including vessels, showing a considerable expression in tumor cells also (mostly in lung and breast cancers). The expression of activated vitronectin in the stroma was less abundant (3/21 colorectal, 22/33 lung, 13/19 breast and 3/10 ovarian). Laminin-5 was mainly located close to tumor cells in basal lamina-like pattern and showed a considerable expression in colorectal, lung and ovarian but not in breast cancers. We conclude that targeting of αvβ3 by cilengitide may exert potent anti-stroma effects as well. The largely varying spatial distributions and expression of integrins and their ligands should be considered in targeting strategies.
Frequency (%) of moderate or strong expression (i.e. in at least 10% of tumor cells) of antigens of interest in human tumors. ColorectalLungBreastOvarya) αvβ3Tumour cells0151620 Stromal cells90685870 Vessels959110070b) αvβ5Tumour cells29587440 Stromal cells9010010070c) VitronectinTumour cells24502140 Stromal cells15656833d) Laminin-5Tumour cells553030 Stromal cells100a / 0b97a / 73b21a / 40b80a / 25baClose to tumor cells; bdistant from tumor cells.
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 2321.