bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4963: ERG expression levels reflect functional status of androgen receptor in prostate cancer
Authors: Dobi Albert , Nydam Timothy , Furusato Bungo , Chen Yongmei , Sesterhenn Isabell , McLeod David G. , Petrovics Gyorgy , Srivastava Shiv 
Published: February 2011

Abstract
Background: Expression of the ERG proto-oncogene, is activated in 50-70% of prostate tumors by androgen receptor (AR) mediated signals due to the fusion of AR regulated promoters (primarily TMPRSS2 and to a lesser extent SLC45A3 and NDRG1) to the ERG protein coding sequence. Our previous studies of quantitative expression levels of ERG or TMPRSS2-ERG fusion transcripts have noted that relatively low or no ERG expression in prostate tumors significantly associated with progressive disease. Here, we have tested the hypothesis that ERG expression levels in prostate tumor cells reflect AR transcriptional regulatory function in a given biological context of the tumor progression. Therefore, tumors with lower ERG may represent a subset with attenuated AR signaling.
Experimental procedures: Expression of ERG and other AR regulated genes were evaluated in a GeneChip dataset obtained from a panel of laser capture micro-dissected well/moderately differentiated (WD) or poorly differentiated (PD) tumor cells derived from primary tumors of patients, who had no prior androgen ablation treatment.
Results: ERG expression pattern was similar to that of other AR regulated genes. Low frequency of ERG expression was noted in PD tumor cells (30%) in comparison to WD tumor cells (80%), suggesting for subdued AR function in a significant fraction of tumors with genomic alterations of ERG.
Conclusions: We developed a cumulative AR Function Index (ARFI) by integrating ERG into a panel of defined AR target genes, may have future potential in stratifying patients for targeted therapy on the basis of overall AR functional status in primary 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 4963.
Abstract 4966: BORIS binding to the promoters of cancer testes antigens, MageA2 and MageA3, causes transcriptional activation of these genes in lung cancer
Authors: Bhan Sheetal , Negi Sandeep S. , Glazer Chad , Chuang Alice , Sun Wenyue , Gaykalova Daria , Shao Chunbo , Ha Patrick K. , Califano Joseph A. 
Published: February 2011

Abstract
BORIS or CTCFL (Brother of the regulator of imprinted sites) is an 11 zinc-finger transcription factor that is involved in epigenetic gene regulation. Boris is normally expressed only in the testes but is aberrantly expressed in many cancers. In the present study, we wanted to study the role of BORIS in the regulation of the cancer testes antigens (CTA) MageA2 and MageA3 in lung cancer. CTAs are also normally expressed in the testes but are upregulated in a variety of cancers like lung, bladder and liver cancers and melanomas. We first investigated the in vivo binding of BORIS to the promoter regions of MageA2 and MageA3 by chromatin immuno-precipitation (ChIP). We found that BORIS was enriched at the promoter regions of these genes in H1299, a lung cancer cell line, compared to the normal lung cell line, NHBE (normal human bronchial epithelial). Interestingly, we found that these genes have high expression in H1299 cell line which is also a high expressor of BORIS. On the other hand, they have very low or no expression in NHBE cells which are also very low BORIS expressors. When BORIS was knocked down in H1299 cells, the expression of these genes was reduced by 25-30%. We then used Luciferase reporter assay to see if MageA2 and MageA3 promoters were activated by BORIS. When BORIS was expressed in the non-expressing cell line NHBE, the activity of the promoters was increased as determined by the luciferase activity. Upon knock-down of BORIS in H1299 cells, the activity of the MageA2 and MageA3 promoters reduced significantly. We further investigated if BORIS binding changes the pattern of histone modification at these promoters. We found that BORIS binding at these promoters in H1299 cells correlates with the enrichment of acetylated H3K9, a modification that is involved in opening up chromatin regions. In the absence of BORIS binding in NHBE cells, methylated H3K9, which is involved with more closed chromatin conformation, is enriched at these sites. These data suggest that BORIS is a positive regulator of the cancer testes antigens and may be a key effector involved in their derepression in lung 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 4966.
Abstract 4967: Changes in c-Myb specificity and activities during the cell cycle in T-ALL and AML
Authors: Quintana Anita M. , Pena Janeth J. , Ness Scott A. 
Published: February 2011

Abstract
The c-Myb transcription factor is a critical regulator of proliferation and stem cell differentiation, and mutated alleles of c-Myb are oncogenic, but little is known about the activities of c-Myb during the cell cycle. Previous studies showed that c-Myb interacts with the cell cycle regulators Cyclin D1 and Cyclin Dependent Kinases 4 and 6, suggesting that c-Myb activity is regulated during the cell cycle. We set out to test that directly, using Chromatin ImmunoPrecipitation (ChIP) assays capable of assessing the activities of c-Myb in primary and flow sorted populations of cells. We performed ChIP assays with cells sorted into each phase of the cell cycle to determine c-Myb specificity and correlated c-Myb occupancy with the relative expression of a number of known target genes. Briefly, asynchronously growing cells were fixed, stained with Hoechst 33342, then flow-sorted into different cell cycle phase populations before processing the samples for ChIP assays. The c-Myb protein associated with different cyclin gene promoters in different stages of the cell cycle, showing that c-Myb specificity and activity are dynamic. By using several different anti-Myb antibodies, we confirmed that the changes were due to relocalization of c-Myb, and not due to changes in the accessibility of individual epitopes. We also analyzed the Myb-regulated CXCR4 gene promoter in both primary AML and Jurkat T-ALL cells. c-Myb occupied the CXCR4 gene promoter during S and G2/M phase of the cell cycle, which correlated with increased CXCR4 expression in cycling cells. In conclusion, our data demonstrate that c-Myb specificity is dynamic, that c-Myb associates with different genes in different phases of the cell cycle and that c-Myb is cell cycle regulated in both T-ALL and primary human AML.
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 4967.
Abstract 4969: Neuropilin-2 is downregulated by Snail during EMT in lung cancer
Authors: Roche Joëlle , Nasarre Patrick , Potiron Vincent , Nair-Menon Joyce , Gemmill Robert , Drabkin Harry 
Published: February 2011

Abstract
Neuropilins (NRP1 and NRP2) are receptors for class-3 semaphorins that are guidance molecules involved in nerve growth patterning, tissue development, immune response, angiogenesis, and cancer development. Upon semaphorin binding, neuropilins transmit signals to the co-receptor, the plexins. Interestingly, neuropilins are also receptors for VEGF. Semaphorins control cell protrusion, spreading and adhesion and can trigger migratory responses often in a repulsive manner but also attractive depending on the cellular context.
We previously cloned SEMA3F, coding for a class-3 semaphorin, in the chromosome 3p21.3 region which undergoes frequent loss of heterozygosity (LOH) in lung cancer. We further reported that levels of SEMA3F inversely correlated with tumor aggressiveness in human lung cancer and we demonstrated the tumor suppressor activity of SEMA3F in experimental xenograft models. In addition, SEMA3F is directly downregulated by ZEB1, a transcription factor involved in the epithelial to mesenchymal transition (EMT).
Recently, we found an inverse correlation between the transcription factor Snail and NRP2 expression in a panel of 19 lung cancer cell lines. Interestingly, Snail is induced during EMT and NRP2 is the best affinity receptor for SEMA3F. Data will be presented with the H358 NSCLC cell line model where Snail induction decreases NRP2 expression both at the RNA and protein levels. Chromatin immunoprecipation (ChIP) experiment suggests Snail direct binding to the NRP2 promoter. In addition, in lung cancer tissue microarrays, Snail and NRP2 stainings are frequently mutually exclusive.
Our results suggest that loss of SEMA3F and NRP2 would trigger EMT and promote metastasis. Therefore, targeting the semaphorin/neuropilin pathway would be an interesting therapeutic approach in lung 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 4969.
Abstract 497: Mitochondria-targeting photosensitizers activable by two-photon absorption
Authors: Ngen Ethel J. , Xiao Lixin , Xingzhong Yan , You Youngjae 
Published: February 2011

Abstract
Two-photon absorption (TPA) is a non-linear optical process, used to activate photosensitizers in the NIR region (700 - 850 nm) thus affording greater tissue penetration in photodynamic therapy (PDT). Since the efficiency of this process has a quadratic dependence on the light intensity, the photodynamic effects are restricted to a small area around the laser's focal point, thus providing spatial selectivity. Although most clinically approved photosensitizers can be activated by TPA, they generally have very small cross-sections (generally below 10 GM around 800 nm). Thus, light intensities required to activate them could damage normal surrounding tissues. The TPA of photosensitizers can however be improved, without perturbing their ability to generate singlet oxygen, by conjugating them to effective TPA chromophores. These then serve as TPA antennae and upon activation transfer their energy to the photosensitizer which then generates singlet oxygen for PDT. In this study a porphyrin-rhodamine B dyad (TPP-Rh), previously demonstrated to target mitochondria, was evaluated as a two-photon photosensitizer for PDT. TPP-Rh, was synthesized by conjugating a monohydroxy porphyrin photosensitizer (TPP-OH) to rhodamine B (Rh B), an effective TPA chromophore, via a saturated hydrocarbon linker, thus enhancing intramolecular FRET between the dyad components and ultimately the photosensitizer's TPA. To evaluate the efficiency of TPP-Rh as a two-photon photosensitizer we studied both its one and two-photon absorption photophysical properties in comparison to those of its individual components: Rh B and TPP-OH. These included: FRET kinetics, FRET dynamics, and the singlet oxygen generation kinetics. A FRET rate of 1.679 × 1012 s−1 and a 99 % FRET efficiency was calculated for TPP-Rh from its spectral properties suggesting efficient FRET from the TPA moiety (Rh B) to the photosensitizer moiety (TPP). In addition to this, TPP-Rh produced singlet oxygen at comparable rates when excited with both TPA at 800 nm and one photon absorption (OPA) at 650 nm. Thus, this indicates that conjugating photosensitizers to rhodamine B could provide several advantages in PDT: deeper tissue penetration, spatial selectivity and selective photosensitizer accumulation.
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 497.
Abstract 4971: WBP2: A novel phospho-oncoprotein in estrogen receptor-positive breast cancer
Authors: Lim Shen Kiat , Prioux Magali Orhant , Tan Kah Yap , Lim Yoon Pin 
Published: February 2011

Abstract
WBP2 (WW-domain Binding Protein 2) was first implicated in breast cancer through our previous phosphoproteomics screen on the MCF10AT xenograft-derived isogenic cell line model of human breast cancer progression, where WBP2 was found to be differentially phosphorylated during breast cancer development. We had also shown it to be an authentic tyrosine phosphorylation target of EGFR signaling. In a follow up study, we found that WBP2 expression was low or undetectable in normal breast epithelial cells but overexpressed in breast cancer progression model as well as multiple breast cancer cells of various subtypes. Therefore, we aimed to investigate the oncogenic role of WBP2 in the growth and progression of human breast cancer through its protein overexpression and tyrosine phosphorylation. We first mapped the EGF-dependent tyrosine phosphorylation sites on WBP2 and identified a member of the Src family of tyrosine kinases as the putative upstream kinase of WBP2. Next, we found that Estrogen (E2) stimulation could similarly induce tyrosine phosphorylation of WBP2 via a crosstalk between EGFR and ER pathways. Subcellular fractionation study revealed a phosphorylation-dependent nuclear entry of WBP2 upon E2 or EGF stimulation. Consistent with the reported role of WBP2 as a coactivator for nuclear hormone receptor (ERα/PR), abrogation of tyrosine phosphorylation on WBP2 significantly impaired the E2-induced ER transactivation through reduced E2/EGF-stimulated nuclear entry of WBP2 and in vivo E2-dependent WBP2-ER interaction. Stable overexpression of wild type and phospho-mimic mutant of WBP2 in ER-positive MCF7 breast cancer cell enhanced its cell proliferation, anchorage-independent growth in soft agar, cell migration and cell invasion in the E2-independent and/or E2-dependent manner. These cellular processes could be inhibited, at least in part, by the phosphorylation-defective mutant of WBP2. Potential mechanisms of WBP2-mediated oncogenic transformation will be presented. Collectively, our findings have uncovered the potential of WBP2 as a novel phospho-oncoprotein in ER+ breast cancer. It is conceivable that WBP2 and/or its tyrosine phosphorylated form could serve as a potential prognostic marker or therapeutic target for human breast 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 4971.
Abstract 4972: Putative mechanism of TAP63α regulation of chondrocyte maturation during long bone development
Authors: Li Feifei , Lu Yaojuan , Abbassi Sam , Ding Ming , Wu Guojun , Wang Siying , Zheng Qiping 
Published: February 2011

Abstract
p63 is the mouse homologue of the well-known tumor suppressor P53. While it remains controversial as to whether P63 functions as a tumor suppressor gene or an oncogene, mouse genetic studies and mutation analysis of human SHFM syndrome (Split Hand/Foot Malformation) have clearly demonstrated that P63 plays an important role in skin and limb development. The truncated limbs observed in p63 null mice suggest that P63 may contribute to long bone development by playing a role during endochondral bone formation. However, how P63 regulates target gene expression and is linked to endochondral ossification remains largely unknown. Here we present some preliminary data suggesting that P63 may regulate type X collagen gene (Col10a1) expression, thereby impacting the process of chondrocyte maturation.
The type X collagen gene (Col10a1) is specifically expressed in hypertrophic chondrocytes, a critical cell stage linking both skeletal development and multiple skeletal diseases. We have previously shown that a 150-bp Col10a1 cis-enhancer is sufficient to mediate its cell-specific expression in vivo. Our further in vitro studies suggest that Runx2, a master transcription factor for osteoblast differentiation as well as for chondrocyte maturation, is one of the major factors that regulate Col10a1 expression via interaction with its tandem repeat Runx2 binding sites. Interestingly, by yeast one-hybrid approach using this cis-enhancer as bait, we identified p53 related proteins as candidate factors that may contribute to the regulation of Col10a1 expression. We have performed Real-time RT-PCR to examine p63 and Runx2 expression in MCT cells, a cell model that shows significant upregulation of Col10a1 upon growth arrest. Both p63 and Runx2 showed around 2-fold upregulation in hypertrophic MCT cells. These data suggest that P63 may collaborate with Runx2 and together regulate Col10a1 expression during chondrocyte maturation. To further explore the putative function of P63 during skeletal development, we have successfully established transgenic mouse lines in which HA and Flag tagged human TAP63α cDNA (the longest P63 isotype) is driven by previously described hypertrophic chondrocyte-specific Col10a1 control element (Col10a1-TAP63α). By phenotypic analysis of these transgenic mice during different developmental stages, we will be able to define the consequence and the potential mechanism of P63 on skeletal development and skeletal disorders.
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 4972.
Abstract 4974: Myc-mediated suppression of the AU-binding protein Tristetraprolin controls Vegf expression
Authors: Rounbehler Robert J. , Li Weimin , Fallahi Mohammad , Cleveland John L. 
Published: February 2011

Abstract
The c-Myc oncoprotein is a transcription factor that drives cell proliferation, apoptosis, and angiogenesis during tumor development. Myc binds to target genes harboring preferred E-boxes to induce their expression, but this response only explains a fraction of the biological responses controlled by Myc. In human Burkitt lymphoma and the B cells and lymphomas of Eµ-Myc transgenic mice, a mouse model of Burkitt lymphoma (BL), Myc induces the expression of Vegf mRNA. Surprisingly, we found that Myc does not bind to the E-boxes found within the Vegf promoter, but rather induces this cytokine by stabilizing its Vegf transcripts. One mechanism that controls the stabilization of Vegf mRNA is the binding of AU-binding proteins (AUBPs) to AU-rich elements (AREs) found in the 3′ untranslated region (3′ UTR) of Vegf mRNA. AREs are present in the 3′ UTRs of approximately 10% of all human genes, including those encoding most of the angiogenic cytokines. Strikingly, expression profiling revealed that Myc regulates ∼30% of ARE-containing genes in human BL and in Eμ-Myc lymphomas. Interestingly, the expression of several AUBPs is altered in premalignant Eμ-Myc B cells, and Myc directly suppresses the expression of the RNA-destabilizing factor Tristetraprolin (TTP). These findings therefore suggest that Myc regulates Vegf expression indirectly, by down-regulating TTP. To directly test the importance of Myc-mediated repression of TTP, we developed Eμ-TTP transgenic mice, to enforce the expression of TTP in the B cells of Eμ-Myc mice. We predict uncoupling Myc's ability to repress TTP will delay tumor development by impairing Vegf expression and thus blocking the angiogenic response. These data provide a novel mechanism whereby Myc indirectly regulates hundreds of ARE-containing genes through the regulation of AUBPs.
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 4974.
Abstract 4975: Dynamic in vivo interactions of the eleven-nineteen lysine-rich leukemia protein (ELL) in the mammalian nucleus
Authors: Wakano Clay , Fufa Temesgen D. , Stasevich Timothy J. , Avery Taara A. , McNally James G. , Gardner Kevin 
Published: February 2011

Abstract
The eleven-nineteen lysine-rich leukemia protein (ELL) is an elongation factor that increases the processivity of RNA polymerase II during transcription. ELL forms a fusion protein with the histone-methyltransferase mixed lineage leukemia protein (MLL) via a chromosomal translocation t(11;19)(q23;p13.1), often associated with acute myeloid leukemia (AML) in both adults and children. This chromosomal translocation alters both proteins, eliminating the carboxyl-terminal methyltransferase domain of MLL and the amino-terminal elongation inhibitory domain of ELL. The biological and regulatory role of normal ELL and ELL in the MLL-ELL fusion protein during transcription is not understood. Transcription is a multi-step process that can be separated into a series of events which involve proteins that form transient and stable complexes with the DNA template at various times during the transcription process. Using the Fluorescence Recovery After Photobleaching (FRAP) approach allows for the dissection of these events in transcription. Transcription in living cells has been examined by photobleaching fluorescently tagged RNA polymerase II, revealing its binding kinetics and quantifying the residency times associated with the different phases of transcription, with shorter residency times correlating with recruitment and initiation and longer residency times with elongation. We have used FRAP to examine the dynamic kinetics of ELL and pol II and other transcriptional elongation factors, including P-TEFb during active transcription in living cells in the presence or absence of specific inhibitors of transcription elongation and initiation. Our results suggest that there is a hierarchy of interactions between elongation factors and pol II during the transcription cycle that is orchestrated through specific interactions with ELL and gives general insights into how disruption of ELL function through its fusion to MLL may selectively influence transcriptional elongation events and gene expression in rapidly growing 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 4975.
Abstract 4982: N-myc downstream-regulated gene 1/Cap43 expression promotes cell differentiation of human osteosarcoma cells
Authors: Fukushima Nobuhiro , Zenmyo Michihisa , Hiraoka Koji , Shoda Takanori , Matsugaki Toru , Komiya Setsuro , Ono Mayumi , Kuwano Michihiko , Nagata Kensei 
Published: February 2011

Abstract
N-myc downstream regulated gene 1 (NDRG1)/Cap43 is closely associated with cell differentiation, and its expression is induced by hypoxia and increasing intracellular calcium. Whether NDRG1/Cap43 expression in cancer cells is a predictive marker of good or poor prognosis in patients depends upon tumor types and differentiation status. In this study, we examined whether NDRG1/Cap43 expression was involved in differentiation of osteosarcoma cells, and used three osteosarcoma cell lines, MG63, U2OS, and SaOS2. Its expression in MG63 and U2OS was significantly enhanced by vitamin D3 that also induced production of osteocalcin, a differentiation marker of osteoblasts. Knockdown of NDRG1/Cap43 using siRNA also suppressed the production of osteocalcin and enhanced cell proliferation, accompanying by suppression of p21 expression. Furthermore, acquired invasiveness of osteosarcoma cells during invasion in Matrigel resulted in decreasing expression of NDRG1/Cap43. A possible role of NDRG1/Cap43 in cellular capacity for differentiation and invasion in osteosarcoma cells will be discussed.
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 4982.