bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4984: Androgen response element of the glycine N-methyltransferase gene is located in first intron
Authors: Lee Cheng-Ming , Yen Chia-Hung , Chen Yi-Ming A. 
Published: February 2011

Abstract
BACKGROUND. The prostrate cancer (PCa) susceptibility gene glycine N-methyltransferase (GNMT) is associated with the metastasis potential of PCa cells. Androgens, which participate in transcriptional regulation via an androgen receptor (AR), play an important role in PCa development. Our two goals were to determine whether GNMT is regulated by androgen, and to map androgen response elements (AREs).
METHODS. Real-time PCR was used to evaluate GNMT mRNA expression levels after LNCaP and DU145 cells were treated with R1881 (a synthetic AR agonist). Putative AREs were identified and tested using the MatInspector program and a luciferase reporter assay respectively. Electrophoretic mobility shift assay and chromatin immunoprecipitation were used to verify the binding properties of the GNMT-ARE motif.
RESULTS. Results from real-time PCR analyses indicate that R1881 is capable of inducing significant GNMT mRNA levels in AR-positive LNCaP cells, but not in AR-negative DU145 cells. According to in-silico screening prediction data, putative ARE1, ARE2 and ARE3 are located within GNMT intron 1, and ARE4 is located within intron 2. According to results from a luciferase reporter assay, only ARE3 mediated the transcriptional activation effects of R1881. Results from an electrophoretic mobility shift assay show that AR binds to ARE3 in vitro. Chromatin immunoprecipitation assay results indicate AR interaction with the ARE3-containing region in vivo.
CONCLUSION. Our data show that GNMT is an AR target gene, with its functional ARE located at +1114/+1128 in GNMT intron 1. We believe this information is valuable for clarifying the relationship between androgen and GNMT gene expression.
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 4984.
Abstract 4986: Urokinase plasminogen activator (uPA) interacts with nuclear HOXA5 and inhibits p53 expression in glioma stem cells
Authors: Gondi Christopher S. , Gorantla Bharathi , Fassett Daniel , Klopfenstein Jeffrey D. , Dinh Dzung H. , Gujrati Meena , Rao Jasti S. 
Published: February 2011

Abstract
Urokinase-type plasminogen activator (uPA) participates in diverse physiological processes, including glioma progression. HOXA5 is a known regulator of p53 expression, and overexpression of HOXA5 has been shown to increase p53 expression. In this study, we have demonstrated that uPA not only translocates to the nucleus but also interacts with the transcription factor HOXA5. We used CD133- and CD44-enriched U87 human glioma cells and 4910 human glioma xenograft cells, which exhibit cancer stem cell properties. Nuclear localization of uPA was determined by western blot analysis of nuclear fractions and by immunocytochemistry. Glioma stem cells showed increased nuclear localization of uPA as compared to normal glioma cells. To determine the in vitro interaction of uPA with HOXA5, we initially used membrane immobilized transcription factors incubated with purified uPA protein and looked for strong protein-protein interactions. We observed that uPA binds preferentially to HOXA5 transcription factor. Subsequently, we immunoprecipitated uPA or HOXA5 from nuclear fractions of U87 and 4910 normal and stem cells and tested for co-precipitation of HOXA5 or uPA respectively. Again, the results showed that uPA binds preferentially to nuclear HOXA5. To determine the effect of uPA or HOXA5 downregulation on these glioma cells, we used RNAi-expressing plasmids targeting uPA or HOXA5. The results showed that downregulation of uPA alone induced overexpression of p53 in both normal and glioma stem cells. Glioma stem cells downregulated for uPA showed at least a 5-fold increase in p53 expression when compared to uPA downregulated normal glioma cells. Downregulation of HOXA5 alone did not show significant change in expression levels of p53; however, simultaneous downregulation of uPA and HOXA5 did not show change in expression levels of p53. To determine whether uPA interacts directly with HOXA5 binding sequences, we performed an electromobility shift assay (EMSA). We observed that uPA does not bind to HOXA5 sequences but rather forms a complex with HOXA5 bound to DNA. In vivo studies showed that subcutaneous tumors injected intratumorally with siRNA-expressing plasmids targeting uPA or HOXA5 either singly or simultaneously showed strong p53 expression in uPA downregulated tumors with no significant change observed in other treatment conditions. Taken together, these results demonstrate that uPA behaves as a negative regulator of p53 expression in glioma cells.
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 4986.
Abstract 4988: Cis-acting genetic variation is associated with altered allele-specific expression of CEBPG transcript in normal human bronchial epithelium
Authors: Blomquist Thomas M. , Brown Ron , Crawford Erin L. , Willey James C. 
Published: February 2011

Abstract
CEBPG (CCAAT/enhancer binding protein gamma) is one of six known members of the CEBP family of bZIP transcription factors. Gene targeted knock-out of CEBPG transcription factor in mice results in early perinatal death, presumably due to observed emphysematous lung histology and abnormal development of alveolar pneumocytes (Kaisho et al, 1999). In recent studies, we observed that: 1) CEBPG transcript expression in normal human bronchial epithelial cells (NBEC) varies greater than 20-fold among individuals (Mullins et al, 2005), 2) the pattern of CEBPG transcript expression in NBEC is different between lung cancer cases and controls (Blomquist et al, 2009), and 3) transcript expression of a key DNA repair gene, ERCC5 (XPG), is partly regulated by CEBPG in NBEC (Crawford et al, 2007). In this study we hypothesized that variation in CEBPG transcript expression patterns in NBEC may, in part, be due to cis-acting genetic variation. In order to test this hypothesis, Allele-Specific Expression (ASE) was measured at transcribed polymorphic site rs2772 in Exon 2 of CEBPG in NBEC cDNA of fifteen individuals heterozygous at rs2772 using allele-specific competitive PCR. ASE at rs2772 was then assessed for association with genotype at the seven polymorphic sites (rs736682, rs17530479, rs17530508, rs1469084, rs16968029, rs3745968, rs36101103) representing the most common haplotypes in the promoter, intron and 3′-untranslated regions of CEBPG gene. CEBPG rs2772 A allele was expressed, on average, 2.34 fold greater than C allele (p &lt; 0.001) in 20% (3 out of 15) of NBEC cDNA samples, among individuals heterozygous at both rs2772 and rs17530479 in the 3′-untranslated and promoter regions of CEBPG, respectively. These findings are consistent with previous reports that in 20% of samples, CEBPG rs2772 A allele was expressed 2.42 fold greater than C allele (Lo et al, 2003). We also observed that 3 out of 9 NBEC samples obtained from individuals diagnosed with lung cancer exhibited rs2772 A:C allelic ratios significantly higher than genomic DNA controls, while 0 out 6 samples from individuals without lung cancer exhibited altered ASE. Of note, rs2772 and rs17530479 polymorphic sites are in linkage disequilibrium with rs10518275 polymorphic site, which was recently associated with severity of cystic fibrosis lung disease (Gu et al, 2009). Here we demonstrate that cis-acting variation in linkage with rs2772 and rs17530479 polymorphic sites is associated with variation in ASE of CEBPG and lung cancer diagnosis.
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 4988.
Abstract 499: EGFR expression correlates with response to photodynamic therapy in esophageal cancer cells
Authors: Yang Pei-Wen , Hung Mien-Chie , Hung Mien-Chie , Wang Ying-Hao , Tung En-Chi , Lee Yung-Chie , Lee Jang-Ming 
Published: February 2011

Abstract
Photodynamic therapy (PDT) has been demonstrated as an effect treatment modality for early esophageal cancer by using a photo-sensitizer which induces a cytotoxic photoreaction in tumor cells after exposure to a specific wave-length of light. However, the mechanism is still poorly understood regarding the response to PDT for the patients with esophageal cancer. Epidermal growth factor receptor (EGFR) activation is known to induce resistance to many anti-cancer treatments. In this study, we intend to investigate the role of EGFR in esophageal cancer treated with PDT. The PDT-induced cell death is based on the accumulation of a photosensitizing drug in specific cells. Followed by irradiation with visible light (usually red light), the drug-accumulation cells will induce apoptosis or necrosis. In our study, we observed PDT induced cell death of human esophageal carcinoma cells, CE48T/VGH in a dose-dependent manner by incubating increasing amounts of photosensitizer photofrin (0 to 20 μg/ml) under the expose of 630 nm red light (0 to 180 mJ/ cm2) by MTT assay. We found the protein expression of EGFR was decreased with increased amounts of photofrin. The phenomenon was more obvious under light treatments. EGFR expression was not recovered in the presence of proteasome inhibitors indicating that the reduction of EGFR was not mediated by proteasome-dependent pathway. However, the amount of EGFR mRNA was similar in PDT treated and un-treated cells by RT-PCR analysis. To further clarify the role of EGFR expression in PDT resistant ECa cells, we selected the PDT resistant esophageal cancer (CE48T/VGH) cells by incubated with 15 μg /ml photofrin under the 54 mJ/ cm2 or 108 mJ/ cm2 of red light exposure. At 25 days post PDT treatment, the cells was collected and indicated as PDTR 1-1 and PDTR 1-2 respectively. Compared to wild type CE48T/VGH cells, PDTR 1-1 and PDTR 1-2 display 16% and 13 % resistances respectively when incubated with 15 μg /ml photofrin under 108 mJ/ cm2 light treatment. Correlated with the resistance, we found that EGFR protein expression was increased in both PDTR 1-1 and PDTR 1-2 (about 18% compared to wild type cells). Based on our preliminary findings, EGFR expression may be involved in PDT resistance in esophageal cancer 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 499.
Abstract 4991: Functional significance of potential oncogene YAP and its isoforms in esophageal squamouse cell carcinoma (ESCC)
Authors: Muramatsu Tomoki , Imoto Issei , Matsui Takeshi , Kozaki Ken-ichi , Tsuda Hitoshi , Shimada Yutaka , Inazawa Johji 
Published: February 2011

Abstract
Previously, we reported cIAP1 to be overexpressed through 11q22 amplification in some ESCC cell lines. YAP, a key molecule in Hippo pathway reported as a possible oncogene in some cancers, locates within the same amplicon in those ESCC lines. Since YAP overexpression was frequently observed in primary ESCC, YAP may work as an oncogene for ESCC. Through expression analyses of mRNA and protein, we identified two novel isoforms of YAP other than two known isoforms. Expression pattern of YAP isoforms was different between normal esophagus and ESCCs, suggesting each isoform to have different function as an oncogene. We constructed stably-transfected cells with siRNA-resistant construct of each of YAP isoforms. We then performed knockdown of endogenous YAP to investigate whether any difference in growth-promoting effect exists among these isoforms. Growth inhibition of ESCC cells with induction of p21 was observed by knockdown of YAP, and each isoform partially rescued siRNA-induced p21 elevation and growth inhibition, although only the small difference was observed among isoforms. Those results suggest that induction of p21 might be regulated by transcriptional repressor YAP, directly or indirectly. Detail analysis of functional significance of YAP will provide not only new avenues for understanding the esophageal carcinogenesis, but also development of YAP-targeted cancer therapy in ESCC.
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 4991.
Abstract 4993: ARHI is required for induction of beclin-1/PI(3)K class III-mediated autophagy
Authors: Lu Zhen , Liao Warren S. L. , Bast Robert C. 
Published: February 2011

Abstract
The maternally imprinted Ras-related tumor suppressor gene Aplasia Ras homolog member I (ARHI; also known as DiRAS3) is downregulated in more than 60% of ovarian cancers. We reported that re-expression of ARHI in vitro at physiologic levels induces autophagy by blocking PI(3)K-Akt signaling and inhibiting mTOR activity, and participated directly in the formation of autophagic vesicles, co-localizing with MAP-LC3-II in the vesicle membrane. Nucleation of autophagic vesicles requires the activity of multi-protein complexes that include Beclin-1 and PI(3) kinase Class III lipid kinase [PI(3)KC3]. A number of proteins have been reported to interact with Beclin-1 and positively or negatively regulate its function in autophagy. One prominent Beclin-1-interacting protein is Bcl-2, which inhibits Beclin-1-dependent autophagy. In this study, we show by indirect immunofluorescence microscopy that ARHI is colocalized with Beclin-1 at the trans-Golgi network. Further, ARHI can be co-immunoprecipitated with Beclin-1 and elimination of ARHI expression by RNA interference compromised Beclin-1-induced autophagy. Concomitant with increased ARHI-Beclin-1 interaction, there was a decreased association between Beclin-1 and its negative regulator Bcl-2. Consistent with its role in Beclin-1-mediated autophagy, knockdown of ARHI also decreased PI(3)KC3 activity, whereas overexpression of ARHI promoted GFP-FYVE co-localization with RFP-LC3. Taken together, our results suggest that ARHI is a positive and necessary regulator of Beclin-1/PI(3)KC3 complex and that ARHI regulates Beclin-1-mediated autophagy by forming a complex at the trans-Golgi network.
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 4993.
Abstract 5: Frequent translocations and overexpression of multiple full-length ETV1 transcripts in prostate cancer
Authors: Gasi Delila , van der Korput Hetty , Trapman Jan 
Published: February 2011

Abstract
In prostate cancer the fusion between TMPRSS2 and the ETS transcription factor gene ERG causes over-expression of truncated ERG. This gene fusion is found in up to 60% of clinical samples. We show that the related gene ETV1 is overexpressed in ∼10% of prostate cancer samples: not only as a fusion transcript with many different partners, but in approximately half of the samples as a full-length transcript. Primary tumors with over-expression of full length ETV1 tend to have a worse prognosis. We showed in a novel fusion event that the complete ETV1 gene is integrated adjacent to the first exon of the poorly characterized ncRNA gene EST14 on chromosome 14. Further characterization of the translocation revealed that not only EST14-ETV1 fusion transcripts were formed, but that also wild-type ETV1 transcripts were over-expressed. These transcripts started at four different alternative first exons and gave rise to production of slightly different ETV1 proteins. However, all proteins have essentially the same properties. Investigation by break-apart in situ hybridization of 7 prostate cancer samples overexpressing full-length ETV1 showed that in at least 5 samples the gene is translocated. This translocation is not to chromosome 14, which seems a hot spot of ETV1 translocations. Chromosome spreads from a xenograft derived from one clinical sample, locate the translocation of ETV1 to a novel site on chromosome 4.
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 5.
Abstract 500: Efficacy of UVC irradiation on GFP-expressing melanoma growth and vascularity in the ear of nude mice
Authors: Aki Ryoichi , Amoh Yasuyuki , Kishimoto Hiroyuki , Kimura Hiroaki , Suetsugu Atsushi , Momiyama Masashi , Katsuoka Kensei , Hoffman Robert M. 
Published: February 2011

Abstract
Our laboratory has developed the use of fluorescent proteins for in vivo imaging (Nature Reviews Cancer 5, 796-806, 2005). We have developed melanoma cell lines that stably express GFP and nude mice that ubiquitously express RFP to study tumor interaction by dual-color imaging. In the present study, we examined the efficacy of UVC irradiation on the growth of murine melanoma expressing GFP in the ear of GFP mice. We also evaluated the efficacy of UVC irradiation against blood vessels vascularizing the melanoma. RFP-expressing blood vessels from transgenic mice expressing RFP used as hosts were readily visible in GFP melanoma. B16F10 melanoma expressing GFP were injected subcutaneously in the ear of the RFP mice. The ears of the mice were observed before and 24 hours after irradiation with UVC. UVC was effective on B16F10 GFP growth and also damaged blood vessels in the tumor. Thus, UVC irradiation has a direct effect on melanoma growth as well as an anti-angiogenesis effect. This dual-color tumor-host model is useful for evaluation of efficacy on melanoma growth and tumor blood vessels, which is readily discernable with fluorescent protein imaging. UVC irradiation is a promising therapeutic for melanoma expressing fluorescent proteins which can be effected in vivo (Proc. Natl. Acad. Sci. USA, 1-6, 14514-14517, 2009).
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 500.
Abstract 5006: Pdcd4 as a prognostic factor and a modulator of cell proliferation, migration and invasion in ovarian cancer
Authors: Wei Na , Liu Stephanie S. , Leung Thomas HL , Tam Kar-Fai , Liao Xiao-yun , Cheung Annie NY , Chan Karen KL , Ngan Hextan YS 
Published: February 2011

Abstract
Programmed cell death 4 (Pdcd4), a novel gene and originally identified as the neoplastic transformation inhibitor, is down regulated in human colon, breast and lung cancer cells and considered as a diagnostic and prognostic marker in lung cancer. It has been shown to have tumor suppressor properties such as inhibition of cell invasion and proliferation, as well as induction of apoptosis. However, those properties of Pdcd4 are tissue specific. The mechanisms of function of Pdcd4 are largely unknown and its function and modulation in ovarian cancer is still elusive. The objectives of our present study are firstly to investigate the expression of Pdcd4 in normal and malignant ovarian tissues and the role of Pdcd4 in ovarian carcinogenesis; and secondly, to study the function of Pdcd4 in the regulation of cell proliferation, migration and invasion and modulation of Pdcd4 in ovarian cancer.
Using both western blot and real-time quantitative PCR analyses, we demonstrated that Pdcd4 expression was continuously down-regulated in the sequence of normal-borderline-malignant ovarian tissue samples. Higher Pdcd4 expression was found to be associated with longer disease-free survival (p=0.037). Using immunohistochemical staining approach, we found the subcellular localization of Pdcd4 differed in the way that, normal ovarian tissues showed distinctive nuclear localization while malignant ovarian tissues showed mainly cytoplasmic staining.
To further explore the function of Pdcd4 in ovarian cancer cells, we developed Pdcd4 over-expression stable clones in ovarian cancer cell lines. Our in vitro studies demonstrated that ectopic Pdcd4 expression significantly inhibited ovarian cancer cell proliferation by inducing cell cycle arrest at G0/G1 stage and the upregulation of cell cycle regulators p27 and p21. The induction of p21 by Pdcd4 was not mediated through p53. Using wound healing, transwell migration and invasion assay, we demonstrated Pdcd4 significantly inhibited ovarian cancer cell migration and invasion.
In conclusion, loss of Pdcd4 was a common abnormality at molecular level in ovarian cancer and it might be a potential prognostic factor in ovarian cancer patients. In addition, our results also provided first evidence for the tumor suppressor properties of Pdcd4 in inhibition of cell proliferation by inducing cell cycle arrest and modulating cell cycle regulators, as well as inhibition of cell migration and invasion in ovarian cancer cells.
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 5006.