bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4965: The epithelial-specific ETS transcription factor ESE1 links inflammation with prostate cancer transformation and progression
Authors: Longoni Nicole , Ortelli Erica , Kunderfranco Paolo , Genini Davide , Grand Maurizia Mello , Chiorino Giovanna , Malek Anastasia , Catapano Carlo V. , Carbone Giuseppina M. 
Published: February 2011

Abstract
Altered expression of ETS transcription factors by chromosomal translocation is a frequent event in prostate cancers. However, deregulated expression of other oncogenic ETS factors can be important for the pathogenesis of this disease. By analyzing the expression of multiple ETS genes in prostate cancer and normal prostate by genomic profiling and quantitative real-time PCR we found that the epithelial-specific ETS factor ESE1 was highly expressed (&gt;4 fold) in 44% of prostate tumors compared to normal prostate. ESE1 has been previously shown to be induced by pro-inflammatory stimuli and to regulate the expression of genes involved in inflammation. Treatment of immortalized prostate epithelial cells (LHS) and prostate cancer cells 22RV1 with the pro-inflammatory cytokine IL-1beta induced ESE1 at RNA and protein levels. Concomitantly we observed that cells acquired ability to grow in poly-hema coated plates and an EMT phenotype. To define the role of ESE1 in prostate cancer progression we established 22RV1 prostate cancer cells stably expressing ESE1 (22RV1-ESE1). ESE1 expressing cells were capable to grow in poly-hema coated plates and when injected in nude mice formed larger subcutaneous tumors compared to control cells. Global gene expression profiles indicate robust changes with many genes differentially expressed in 22RV1-ESE1 cells compared to control cells, including key genes involved in cell invasion and metastasis such as COX2 and MMP-10. Consistently, 22RV1-ESE1 cells had greater ability to migrate compared to parental cells in Boyden Chamber and wound-healing assays. Furthermore, when implanted in mice via tail vein injection, 22RV1-ESE1 cells displayed greater ability to form lung metastasis compared to control cells. These results suggest that ESE1 contribute to the acquisition of transforming properties such as the ability to invade and metastasize. Induction of ESE1 during chronic inflammation could be an essential step for prostate cancer initiation and may co-operate with other ETS alterations for 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 4965.
Abstract 4981: ICI182,780 induces P-cadherin upregulation in breast cancer cells through histone modifications at the promoter level: The role of C/EBPbeta in CDH3 gene activation
Authors: Albergaria André , Ribeiro Ana Sofia , Pinho Sandra , Milanezi Fernanda , Carneiro Vítor , Sousa Bárbara , Sousa Sónia , Oliveira Carla , Machado José Carlos , Seruca Raquel , Paredes Joana , Schmitt Fernando 
Published: February 2011

Abstract
P-cadherin is a classical cadherin which has been extensively studied concerning its functions and its prognostic value in breast cancer. Moderate to intense expression of P-cadherin has been identified in 30% - 50% of invasive ductal carcinomas of the breast, being reported to be strongly associated with proliferative and high histological grade, decreased patient survival and as a marker of the aggressive behaviour of basal-like and HER-2 tumour subtypes. In vitro, P-cadherin overexpression is also able to induce increased cell invasion and migration. However, only a few works have been published in order to decipher the regulatory mechanisms behind P-cadherin overexpression in breast cancer. P-cadherin is up-regulated by the antiestrogen ICI 182,780, suggesting that the lack of ERalpha signalling may be responsible for the aberrant P-cadherin expression in breast cancer, but the mechanisms underlying this ICI-induced aggressive behaviour are completely unknown. The aim of this study was to determine whether the induction of the CDH3 gene is a direct effect of ICI 182,780 at CDH3 promoter level or would require the prior induction of other genes/proteins or epigenetic mechanisms.
We found that ICI 182,780 increases CDH3 promoter activity as well as induces an epigenetic mechanism that lead to activating histone modifications at putative C/EBPbeta binding sites in at the CDH3 promoter. We also demonstrate that this transcription factor is able to directly activate P-cadherin transcription in breast cancer cells and that these two proteins are highly associated in human breast carcinomas, being both significantly related with high grade and proliferative invasive breast carcinomas. This study brings forward the characterization of putative intracellular pathways and epigenetic mechanisms that are able to induce P-cadherin overexpression in breast cancer cells and, in general, contribute to clarify the ability of ICI 182,780 to induce expression of signal transduction genes normally repressed by oestrogen/ER signalling. In addition, we showed for the first time that the transcription factor C/EBPbeta is able to regulate P-cadherin overexpression in breast cancer.
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 4981.
Abstract 4985: Identification of PARP-1 as a novel KLF8 interacting and regulating protein
Authors: Lu Heng , Wang Xianhui , Urvalek Alison M. , Li Tianshu , Yu Lin , Zhu Jinhua , Lin Qishan , Zhao Jihe 
Published: February 2011

Abstract
KLF8 transcription factor regulates important genes including cyclin D1 and E-cadherin and plays a critical role in cell cycle progression, oncogenic transformation and EMT. Transcription factors need to interact with both DNA and other proteins in order to regulate transcription. However, little is known about KLF8-protein interaction. Using mass spectrometry and co-immunoprecipitation (co-IP), we identified PARP-1, a chromatin-associated enzyme that catalyzes protein poly(ADP-ribosyl)ation (PARylation), as one of novel proteins that interact with KLF8. Co-IP and western blotting indicated that KLF8 is a PARylation substrate. Mutation of the cystein residues in the first and second zinc-finger motifs of KLF8 abolishes its interation with PARP1. Luciferase assays showed KLF8 activation on the cyclin D1 promoter was significantly reduced when PARP1 was physically deleted or functionally inhibited or when KLF8-PARP-1 interation was disrupted. Surprisingly, immunofluorescent staining demonstrated that KLF8 was localized in the nuclei of the wild-type mouse embryonic fibroblasts (MEF), but was mislocalized in the perinuclear cytoplasm of the PARP-1−/− MEFs, which could be rescued by re-expression of PARP1. Interestingly, while the PARP1-interation deficient KLF8 mutant was also mislocalized in the cytoplasm of the wild-type MEFs, inhibition of PARP1 activity in the MEFs did not affect the nuclear localization of wild-type KLF8. Cychloheximade (CHX)-chase assay revealed the stability of KLF8 dramatically reduced by loss of PARP-1 or when KLF8-PARP-1 interaction was disrupted. Ubiquitination assay showed heavier ubiquitin chains in PARP-1−/− MEFs or when KLF8-PARP-1 interaction was disrupted. Furthermore, DNA damage assay under Doxorubin treatment indicated KLF8 involved in PARP-1-dependent DNA damage repair pathway. Those results suggest that PARP-1 work as a co-activator in KLF8's transcriptional activity on Cyclin D1 promoter, keep KLF8's nuclear localization, inhibit KLF8's ubiquitination and contribute to KLF8's stability. This work has identified PARP1 as a novel binding partner and post-translational modifier of KLF8 and a critical regulator of KLF8 localization, function and stability in the 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 4985.
Abstract 4989: FLIP transcriptional deregulation: A potential mechanism for development of androgen independent prostate cancer
Authors: Xie Jianping , Ghosh Rita , Kumar Addanki P. 
Published: February 2011

Abstract
The cellular Fas/FasL-associated death domain protein-like inhibitory protein (c-FLIP) plays a critical role in the regulation of apoptosis. Studies from our laboratory identified transcription factor Sp1 as an activator and Sp3 as an inhibitor of Sp1 transactivation of FLIP in prostate cancer cells. We have also shown that inhibition of FLIP by 2-methoxyestradiol (2-ME2) (i) induces apoptosis in prostate cancer cells and (ii) is associated with regression of prostate tumors in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. In addition FLIP promoter contains putative binding sites for various transcription factors including AP-1, c-Myc, NFκB, ARE (androgen response element) and p53, it is possible that these elements alone or through cooperative interactions may be important for the regulation of FLIP transcription and also in mediating 2-ME2 induced apoptosis. The present study was carried out to investigate the role of androgens in the transcriptional regulation of the FLIP using deletion analysis coupled with chromatin immunoprecipitation assay (ChIP), electrophoretic mobility shift assay (EMSA) and transient expression assays in prostate cancer cells. Our results show that treatment of androgen responsive LNCaP cells with DHT stimulates (i) cell proliferation; (ii) FLIP transcriptional activity; (iii) Sp1 and ARE DNA binding activity; (iv) PSA transcriptional activity and treatment with 2-ME2 inhibited the observed DHT-stimulated activities. Our findings suggest that although the FLIP promoter binds multiple nuclear proteins, Sp1 or a related protein appears to be a critical determinant of FLIP transcription, possibly through cooperative interactions between Sp1 and additional transcription factors including AR. Supported by ACS RSG-04-169 and NIH CA 135451 (APK).
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 4989.
Abstract 4990: Nuclear Factor-Y (NF-Y) regulates the transcription of the human aldo-keto reductase 1C1 (AKR1C1) gene*
Authors: Rajash Pallai , Simpkins Henry , Chen Jianli , Parekh Hemant K. 
Published: February 2011

Abstract
Dihydrodiol dehydrogenases are a family of aldo-keto reductases (AKR1Cs) involved in the metabolism of steroid hormones and xenobiotics. Here, we have cloned and characterized the proximal promoter region of the human AKR1C1 gene. The 5′ flanking proximal promoter region of the AKR1C1 gene consists of a TATA box and an inverted CCAAT binding site. Deletion analysis of the 5′-flanking, ∼3.0 kb region of the human AKR1C1 gene, identified the region between −128 to −88 as the minimal proximal promoter that is essential for basal transcription of AKR1C1 in human ovarian (2008 & 2008/C13*), lung (H23 & A549) and liver carcinoma (HepG2) cells. Based on computational analysis, a set of potential putative transcription factor binding sites for Oct1, Sp1, NF-Y, C/EBP, p40X, USF, NF1 and AP-2 were identified in this region. Site-directed mutagenesis studies indicated that the transcription factor binding sites for NF-Y/CEBP were essential for controlling the basal transcription of AKR1C1 in all the cancer cells studied. Electrophoretic mobility shift (EMSAs) and gel supershift assays demonstrated that the transcription factor NF-Y preferentially binds to the inverted CCAAT box at −109ATTGG−105 of the AKR1C1 gene. These results indicate that the NF-Y transcription factor regulates the basal transcription of AKR1C1 in human ovarian, lung and liver carcinoma 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 4990.
Abstract 4998: Down-regulation of Hsulf-1 promotes tumorigenicity of ovarian cancer cells
Authors: He Xiaoping , Ohta Tsuyoshi , Shridhar Viji 
Published: February 2011

Abstract
Human Sulfatase1 enzyme (HSulf-1) is down-regulated in a majority of ovarian cancer cell lines and primary tumors, but the functional consequence of this downregulation remains unclear. Here, we showed that down-regulation of HSulf-1 by RNA interference in OV202 ovarian cancer cells resulted in an elevated level of phosphorylated AKT. Conversely, over-expression of HSulf-1 in SKOV3 ovarian cancer cells led to decreased phosphorylation of AKT. When cells were treated with CDDP, OV202 cells with knockdown of HSulf-1 displayed more resistance to drug-induced apoptosis, with IC50 value 3-fold higher than cells with non-targeting shRNA, while SKOV3 cells with overexpression of HSulf-1 were more sensitive to drug-induced apoptosis compared to the control cells. Moreover, knockdown of HSulf-1 also endowed ovarian cancer cells with increased resistance to detachment-induced apoptosis (anoikis). Cell proliferation assays revealed that knockdown of HSulf-1 significantly accelerated cell proliferation of ovarian cancer cells in vitro. Importantly, when cells were injected subcutaneously, 7 of 8 (87.5%) nude mice developed tumors with HSulf-1 knockdown cells within 2 weeks. However, none of the mice injected with nontargeted control transduced cells (control group) developed tumors. Four weeks after injection, 8 of 8 (100%) nude mice developed tumors with HSulf-1 down-regulated cells, while only 2 of 5 (40%) mice had tumors in the control group. The average tumor weight was 4.2±2.7g per mice in HSulf-1 knockdown group, significantly higher than 0.6±0.3g per mice in the control group. Collectively, these results strongly suggest that down-regulation of HSulf-1 promotes tumorigenicity of ovarian cancer possibly due to elevated activation of AKT pathway.
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 4998.
Abstract 5004: Functional modulation of insulin-like growth factor binding protein-3 in melanoma
Authors: Dar Altaf A. 
Published: February 2011

Abstract
Insulin-like growth factor binding protein-3 (IGFBP3) is a member of the IGFBP family, which regulates the mitogenic and anti-apoptotic effects of insulin-like growth factors. Hypermethylation of the IGFBP3 promoter has been found to suppress its expression in different tumors. In the present study we evaluated the role of IGFBP3 in melanoma. Quantitative real time PCR (qRT-PCR) of 12 melanoma cell lines indicated a significant down-regulation of IGFBP3 expression as compared to a normal melanocyte cell line. qRT-PCR of human melanoma tissues showed significant downregulation of IGFBP3 as compared to nevus samples. Melanoma cell lines treated with the demethylating agent 5-AZA-2′deoxycytidine (5AZA) re-expressed IGFBP3 at the mRNA level, indicating a possible role for methylation in the suppression of its expression. We examined the methylation status of the IGFBP3 promoter in cell lines and in human tissue samples by bisulfite DNA sequencing. The promoter region of IGFBP3 in C8161.9 and DO4 melanoma cell lines was hypermethylated, which was completely reversed by treatment of these cells with 5AZA. The IGFBP3 promoter region was also highly methylated in human melanoma samples as compared to normal nevus samples. Overexpressing IGFBP3 in melanoma cells in vitro suppressed cell survival and colony formation and increased rate of apoptosis. Stable overexpression of IGFBP3 suppressed melanoma cell growth in vivo. Our results indicate that silencing of IGFBP3 in melanoma is due to the methylation of its promoter, and overexpression of IGFBP3 induces apoptosis and suppresses cell survival and growth.
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 5004.
Abstract 5020: Role of LIN28 in aggressive breast cancers lacking REST
Authors: Gunsalus Kearney T.W. , Wagoner Matthew P. , Potter Wyatt B. , Schoenike Barry , Roopra Avtar 
Published: February 2011

Abstract
Our lab has discovered a highly aggressive subset of breast cancers characterized by a lack of function of the tumor suppressor RE1 Silencing Transcription Factor (REST). REST is a transcriptional repressor controlling over 2000 neuronal genes, and has been identified as a tumor suppressor in lung and colon cancers. Our lab has discovered that REST function is lost in 20% of breast tumors and that its loss is associated with a significantly decreased disease-free survival and poor prognosis (Wagoner et al. poster, this meeting, CB4).
In addressing the mechanisms underlying the aggressiveness of these RESTless tumors, we found that expression of the tumor promoter LIN28 is upregulated. We describe the direct regulation of LIN28 by REST in a range of mammary cell lines and show a correlation between REST loss and LIN28 overexpression in breast tumors. LIN28 inhibits maturation of the tumor suppressor microRNA let-7, which in turn suppresses expression of the oncogenes Myc and Ras. LIN28 overexpression has been found to promote metastasis in a mouse xenograft model of breast cancer.
To examine the effects of REST loss and LIN28 expression on cellular transformation and motility, we have knocked down REST and LIN28 in a variety of breast cell lines (including T47D, MCF7, MDA-MB-231, 3T3 and NMuMG cells). Here, we describe the results of our colony formation, soft agar growth and motility assays. We recapitulate in vitro aspects of tumor aggression seen in the patient population, and we find that these processes are promoted by REST loss in a LIN28-dependent manner. We also describe xenograft models looking at the growth and metastasis of tumors that express or lack REST and LIN28. We conclude that REST loss promotes tumor aggressiveness at least in part via upregulation of its target gene LIN28.
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 5020.
Abstract 5030: Mechanistic insight of differential sensitivity to MEK inhibition
Authors: Ji Zhenyu , Njauw Ching-Ni , Tsao Hensin 
Published: February 2011

Abstract
BRAF is mutated in melanomas and plays a role in tumorigenesis. Although depletion of oncogenic BRAF resulted in tumor regression in mouse melanoma model, clinical development of anti-BRAF signaling therapy has not been successful up to date. We performed a search of genomic alterations that are correlated to sensitivity to MEK inhibitors using human melanoma cell lines. Multiple genetic changes are identified to be of predictive value. Based on our genetic analysis, p53 is identified to be a major factor that controls sensitivity to MEK inhibitors. p53 is a major tumor suppressor and is mutated in a small set of human melanomas. Here, we show that p53 is inducible in most human melanoma cell lines in response to DNA damage. MDM2 inhibitor Nutlin-3a increases p53 protein expression as well as its activities in melanoma cells. Addition of nutlin-3a significantly increases sensitivity of melanoma cells to MEK inhibitor U0126 induced cell death or cell cycle arrest. In addition, knockdown p53 by specific shRNAs effectively rescues apoptosis induced by MEK inhibitor and/or p53 activation. This data suggests that p53 activity is required for cell death induced by MEK inhibitors and/or p53 activators. In conclusion, p53 is identified from a genetic screen for MEK inhibitor sensitivity. p53 reactivation potentiates cell death induced by BRAF/MEK signaling inhibitory agents in a group of melanomas.
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 5030.
Abstract 5042: Trop-2 is a universal cancer growth stimulator through a ubiquitous signaling platform
Authors: Alberti Saverio , Trerotola Marco , Guerra Emanuela , Havas Kristina , Lattanzio Rossano , Lasorda Rossana , Bonasera Veronica , Vacca Giovanna , Aloisi Anna Laura , Piantelli Mauro 
Published: February 2011

Abstract
Trop-2 is a transmembrane calcium signal transducer. Our findings show that Trop-2 is overexpressed by the majority of human cancers, suggesting strong selective pressure for a conserved function. Trop-2 was then demonstrated to be necessary and sufficient to stimulate cancer growth, with a linear relationship between growth rates and Trop-2 expression levels. Cell growth stimulation was shown to be conserved across cell-types and species. These findings indicated impingement on a ubiquitous downstream signal-transduction module. The Trop-2 signaling pathway was investigated by yeast 2 hybrid screening, coimmunoprecipitation / mass-spectrometry and proteomic chip analysis. Trop-2 was demonstrated to bind CD44 and tetraspanins, triggering their growth-promoting ability via a feed-forward activation loop of CD9-recruited PKCα and phosphorylation of the Trop-2 cytoplasmic tail. We demonstrate that PKCα stimulates growth in a Trop-2-restricted manner and that PKCα and Trop-2 are coordinately transported in recurrent waves to membrane ruffles and podosomes. Trop-2 induction was shown to activate the ERK pathway, to up-regulate NF-κB, and to modulate apoptotic factors, including p53 and Rb. Members of the Trop-2 pathway (CD9, CD44 and p53) were found coordinately upregulated in retrospective studies of human cancer case series. These findings reveal the existence of a novel, strikingly widespread mechanism of stimulation of cancer growth. This is quantitatively driven by a wild-type Trop-2 and acts upon ready-to-signal, ubiquitous signal-transduction platforms.
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 5042.