bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4576: Hepatocyte nuclear factor 4 alpha suppresses cell proliferation and induces cellular senescence and apoptosis in prostate cancer cells
Authors: WANG Zhu , Chan Franky Leung 
Published: July 2016

Abstract
Hepatocyte nuclear factor 4α (HNF4α, NR2A1) is a highly conserved member of the nuclear receptor superfamily of ligand-dependent transcription factors. Recent advances show that it is a key transcriptional regulator of many genes, involved in xenobiotic and drug metabolism and also cancers of gastrointestinal tract. However, the exact functional roles of HNF4α gene in prostate cancer progression are still not fully understood. In this study we used the overexpression (gain-of-function) and knockdown (loss-of-function) approaches to determine the functional roles of HNF4α in prostate cancer. Our results showed that HNF4α exhibited a reduced expression pattern in many prostate cancer cells compared to immortalized prostatic cell lines. Its overexpression could significantly inhibit the cell proliferation of prostate cancer cells, and trigger the cellular senescence and apoptosis by activation of p21 signal pathway in a p53-independent manner. We showed that stable overexpression of HNF4α could significantly induce G2/M arrest in PC3 cells, while shRNA-mediated knockdown of HNF4α could induce G1 growth arrest, suggesting that HNF4α might play a negative role in the cell cycle regulation of PC3 cells. Moreover, stable HNF4α knockdown could confer resistance to paclitaxel treatment and enhance colony formation capacity in prostate cancer cells. Together, our results suggest that HNF4α may play a tumor suppressor function in prostate cancer progression.This work was supported by a Direct Grant for Research 2015-2016 (2015. 1. 064), CUHK.
Citation Format: Zhu WANG, Franky Leung Chan. Hepatocyte nuclear factor 4 alpha suppresses cell proliferation and induces cellular senescence and apoptosis in prostate cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4576.
Abstract 4588: Estrogen receptor alpha mediates HPV E6/E7 oncoproteins: Induced breast cells proliferation
Authors: McGhee Eva , Tran Lucy , Li Mengtao , Wu Yong , Chung Seyung , Araniego Cheryl , Tate Karen , Baker Melanie , Evans Kamilah , Rouse Mechelle , Vadgama Jay 
Published: July 2016

Abstract
The association of human papillomavirus (HPV) with cervical cancer, head and neck cancer is well established, but the involvement of HPV E6/E7 oncoproteins in breast cancer is more contentious. Previous studies suggest that high risk HPV E6/E7 oncoproteins inactivate two tumor suppressor proteins p53 and pRb signaling and increase cell proliferation. There is cumulative evidence that high risk HPV 16 E6/E7 oncoproteins may have causal roles in some human breast cancers. Moreover, some studies have identified HPV DNA in breast tissue and breast cancer specimens. Nevertheless, the route of transmission of HPV in breast cells has not been determined, and the mechanisms by which HPV involvement in breast cancer are not known. We used a non-tumorigenic (MCF12A) epithelial breast cell line transfected with HPV 16 to elucidate the role of oncoproteins E6/E7 in pro-proliferative and anti-apoptotic signaling pathways. We also used Tamoxifen treatment, which is an antagonist of the estrogen receptor in breast tissues through its active metabolite, 4hydroxytamoxifen. We demonstrate that HPV E6/E7 transfection activates the extracellular signal-regulated kinase (ERK) MAPK pathway and Akt/PKB kinase signaling pathways through activating estrogen receptor alpha in MCF12A cells. E6/E7 oncoproteins transfection alone dramatically increases estrogen receptor alpha protein expression. Treatment with tamoxifen, an antagonist of the ER, significantly abolishes E6/E7-increase in ERK and PKB phosphorylation without altering their protein levels, suggesting that the estrogen receptor is a key mediator of HPV E6/E7 mediated ERK and Akt/PKB activation. Our current work show an insightful understanding of the molecular mechanisms of HPV-elicited Akt/PKB activation and its roles in cell proliferation and survival in normal breast epithelial cells. Therefore, these findings indicate that HPV E6/E7 oncoproteins may promote the transforming activities of high-risk HPV E6/E7 proteins and cell proliferation in breast cells. Therefore, suppression of estrogen receptor signaling networks may be used as a therapeutic strategy for HPV associated lesions and cancers such as breast metastasis.
Citation Format: Eva McGhee, Lucy Tran, Mengtao Li, Yong Wu, Seyung Chung, Cheryl Araniego, Karen Tate, Melanie Baker, Kamilah Evans, Mechelle Rouse, Jay Vadgama. Estrogen receptor alpha mediates HPV E6/E7 oncoproteins: Induced breast cells proliferation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4588.
Abstract 4593: Analysis of transforming growth factor β receptor trafficking on different signaling transduction pathways
Authors: Ng Evelyn , Di Guglielmo John 
Published: July 2016

Abstract
Transforming growth factor beta (TGFβ) is a cytokine that regulates cellular adhesion, proliferation and apoptosis. Its canonical downstream effectors include receptor-regulated Smad2/3 proteins, which are phosphorylated and then translocated to the nucleus to alter transcription. Additionally, other atypical pathways are simultaneously initiated by TGFβ, including that of p38 (a mitogen activated protein kinase).
TGFβ acts as a tumour suppressor in its normal epithelial environment, but in tumor cells, it promotes epithelial-mesenchymal transition and cell migration. The manner in which tumor cells overcome the growth suppressive effects of TGFβ is not well-understood, especially since downstream TGFβ signaling is still apparent in these cells. This may point to selective pathway activation as a reason for its dual roles. Thus, it is important to consider membrane trafficking—a central process that directs signaling between various cascades.
Previous studies from our lab demonstrate that perturbation of aPKC signaling alters TGFβ receptor trafficking and Smad signal transduction. Furthermore, we have also observed increased access to the p38 MAPK pathway in cells that have been silenced for aPKC expression. We are currently assessing the trafficking of the TGFβ receptor complex in order to investigate the mechanism(s) responsible differential access to specific signaling pathways. This will be addressed using techniques such as co-immunoprecipitation, immunofluorescence microscopy, subcellular fractionation and western blotting.
Determining these mechanisms will further our understanding on cancerous TGFβ pathway regulation, and may lead to the discovery of promising therapeutic targets.
Citation Format: Evelyn Ng, John Di Guglielmo. Analysis of transforming growth factor β receptor trafficking on different signaling transduction pathways. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4593.
Abstract 4594: Involvement of receptors tyrosine kinase in the modulation of store-operated calcium entry
Authors: Emeriau. Noémie 
Published: July 2016

Abstract
A multitude of studies show that alterations in Ca2+ signalling initiate or support the development of hallmarks of cancer. In particular, the role of store-operated Ca2+ entry (SOCE) in tumorigenesis and tumour progression has been subject to intense investigation. SOCE is the main mechanism by which external Ca2+ enters into the cell. It is initiated by depletion of ER Ca2+ stores and mediated by several proteins such as STIM1, an ER transmembrane protein sensing Ca2+ within the ER and ORAI1, a plasma membrane Ca2+ channel. We recently showed that SOC inhibition interfered with EGFR-dependent signalling in non-small cell lung carcinoma cells.
In this study, we observed that STIM1 depletion reduced neuregulin-dependent proliferation of breast cancer cells. Since neuregulin binds to ErbB3 and/or ErbB4 and therefore activates ErbB2, this result prompted us to investigate whether ErbB proteins might modulate SOCE. We observed that lapatinib, a dual inhibitor of EGFR and ErbB2, dramatically inhibited SOCE. As expected, lapatinib also inhibited phosphorylation of EGFR, ErbB2 and downstream pathways of both receptors. Specific inhibition of EGFR by erlotinib or gefitinib had no effect on SOCE. In contrast, specific inhibition of ErbB2 by CP724714 mimicked the effects of lapatinib. We also investigated the role of downstream pathways of ErbB2 in the modulation of SOCE. Inhibition of the MAPK and the JAK-STAT pathways does not modify the amplitude of SOCE. Contrariwise, LY294002 and MK2206, two inhibitors of the PI3K pathway, dramatically reduced SOCE. Interestingly, in silico analysis showed that STIM1 might be phosphorylated by Akt.
All these results suggest that SOCE is important in the proper function of ErbB2-dependent signalling. This raises the possibility to target molecular mediators of SOCE in order to interfere with the proliferation of cancer cells.
Citation Format: Noémie Emeriau. Involvement of receptors tyrosine kinase in the modulation of store-operated calcium entry. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4594.
Abstract 4595: Development and validation of a novel EGF receptor-neutralizing monoclonal antibody
Authors: Zuberek Hincman Krystyna , Manning Christopher A. , Nelson Michael R. , Lewis Michael , Scialdone Roy , Darce Jaime , Lutz Stephen R. , Burford Evans , Haack Herbert , Silver Matthew R. 
Published: July 2016

Abstract
The epidermal growth factor receptor (EGFR) is a cell-surface receptor for members of the epidermal growth factor family (EGF-family). EGFR dimerizes upon ligand binding, which leads to autophosphorylation, downstream signaling and ultimately internalization. In cancer, EGFR mutations and amplification have been linked to cell proliferation and survival. Two EGFR neutralizing monoclonal antibodies are currently FDA approved, which includes Cetuximab (Erbitux, BMS; mouse/human chimeric) and Panitumumab (ABX-EGF, Amgen; fully humanized). However, these antibodies are often unavailable to researchers studying this important pathway. Here we describe the development and validation of a new rabbit monoclonal EGFR neutralizing antibody (clone D1D4J). D1D4J was validated using cell-based models and immunofluorescence imaging. D1D4J binds EGFR and neutralizes EGF-induced activation and internalization. Compared to other Research Use Only (RUO) neutralizing antibodies on the market, D1D4J shows superior performance and is a useful research tool in the EGFR signaling space.
Citation Format: Krystyna Zuberek Hincman, Christopher A. Manning, Michael R. Nelson, Michael Lewis, Roy Scialdone, Jaime Darce, Stephen R. Lutz, Evans Burford, Herbert Haack, Matthew R. Silver. Development and validation of a novel EGF receptor-neutralizing monoclonal antibody. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4595.
Abstract 4599: Bile acids modulate estrogen receptor β signaling through nongenomic actions in colorectal cancer
Authors: Trujillo Jesse 
Published: July 2016

Abstract
Bile acids deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) have contrasting effects on tumor development. DCA is measurable at increased levels in the serum of colorectal adenocarcinoma patients and is associated with disease progression. DCA is also a well-established tumor promoter. On the other hand, UDCA is a chemopreventative agent revealed to suppress the recurrence of highly dysplastic polyps in a phase III clinical trial. Remarkably, retrospective investigation of the data had shown that UDCA's efficacy as a chemopreventive mediator was gender specific. UDCA significantly lowered the recurrence of advanced lesions in males, but caused a significant increase in the recurrence of advanced lesions in females. Our lab is in pursuit of understanding the gender specific chemopreventive role of UDCA. Estrogen receptor β (ERβ) has been shown to play a significant role in controlling the development of colorectal cancer. Therefore, we hypothesized that the altered regulation of the ERβ pathway by UDCA might explain the gender specificity of this molecule. In order to assess this, we analyzed the effects of UDCA on ERβ to those of the known tumor promoter DCA in both male and female human adenocarcinoma cell lines. Female HT-29 colorectal adenocarcinoma cells induced the phosphorylation of ERβ, as well as up-regulated gene expression of estrogen response elements (EREs), showing stimulated activity of this hormonal receptor. Moreover, we found that pre-treating the cells with PD98059, a MEK 1/2 inhibitor, UDCA and DCA-induced phosphorylation of ERβ, along with increased ERE gene expression, was significantly reduced. Collectively, this data suggests that UDCA and DCA can stimulate ERβ signaling through the non-genomic MAPK signaling cascade; suggesting that UDCA's gender-specific effects may be due, in part, to signaling through hormone receptors.
Citation Format: Jesse Trujillo. Bile acids modulate estrogen receptor β signaling through nongenomic actions in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4599.
Abstract 4601: Regulation of Hes1 expression by the Wnt transcription factor T-cell factor-4
Authors: Koga Hironori , Imamura Yasuko , Ikezono Yu , Wada Fumitaka , Nakamura Toru , Iwamoto Hideki , Masuda Atsutaka , Sakaue Takahiko , Yano Hirohisa , Torimura Takuji 
Published: July 2016

Abstract
Background: The Notch effector Hes1 plays a critical role in stemness of cancer stem cells (CSCs). T-cell factor (TCF)-4 is a key transcription factor in Wnt signaling, which is suggested to be linked with Notch signaling. Among our TCF-4 isoforms cloned previously, the TCF-4J and K pair have been characterized based on the presence (K) or absence (J) of SxxSS motif (Exp Cell Res 2010). TCF-4J was highly expressed in poorly differentiated human hepatocellular carcinoma (HCC) tissues, and the TCF-4J-overexpressing HCC cells (J cells) exhibited high tumor-initiating potential, which is one of the features of CSCs (PLoS One 2013). Thus, the AIM of this study was to investigate whether the SxxSS motif of TCF-4 was involved in the regulation of Hes1 expression in HCC cells. Methods: TCF-4K mutants were prepared by site-directed mutagenesis. Sphere formation assay was used to condense CSC-like cells. Results: Hes1 was strikingly expressed in spheres of J cells and K-mutant cells in both protein and mRNA levels, while its expression level was 70% inhibited in K cells. Consistently, protein expression levels of Jagged1 and Notch1 were highest in J cells under both attached and floating conditions. The Notch inhibitor DAPT, a γ-secretase inhibitor, clearly decreased the expression levels of Hes1, suggesting that the Notch-Hes1 axis was functional. Conclusion: Lack of SxxSS motif in TCF-4 robustly upregulated Hes1 expression in HCC cell spheres. The finding strongly suggests that TCF-4 directly regulates Hes1 in HCC spheres, where CSCs abundantly exist.
Citation Format: Hironori Koga, Yasuko Imamura, Yu Ikezono, Fumitaka Wada, Toru Nakamura, Hideki Iwamoto, Atsutaka Masuda, Takahiko Sakaue, Hirohisa Yano, Takuji Torimura. Regulation of Hes1 expression by the Wnt transcription factor T-cell factor-4. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4601.
Abstract 4604: Activities of in vitro prepared recombinant wnt inhibitory factor-1 (Wif-1)
Authors: Babaer Duaa A. , Wang Xiaofei 
Published: July 2016

Abstract
Wnt Inhibitory Factor-1 (Wif-1) is a secreted modular protein that inhibits the activities of Wnt signaling pathway. The latter is involved in many aspects of cancer and embryonic development. Many studies have shown that reduced WIF-1 expression is associated with the development of cancer. Since WIF-1 acts in extracellular space, it is possible to use in vitro expressed WIF-1 as a therapeutic agent for cancer treatment. We tested whether in vitro expressed recombinant WIF-1 could elicit inhibitory effects on Wnt pathway in 3T3 cells by examining the expression of insulin-like growth factor II (Igf2), Wnt1 inducible signaling pathway protein 2 (Wisp2), (C/EBPδ), and peroxisome proliferator-activated receptor γ (PPARγ) which has been implicated as a suppressor in numerous cancer types including human breast, lung, and colon cancer. 3T3 cells were treated with 0, 1, 5 and 20 ng/ml of recombinant mouse Wif-1 protein. Total RNA was isolated after 24-48 hours of treatment. The levels of Igf2, Wisp2, C/EBPδ, and PPARγ mRNA were analyzed with reverse transcription quantitative polymerase chain reaction. Results are being analyzed to determine whether the in vitro expressed recombinant Wif-1 protein can modulate the expression of these genes and regulate cancer to have a significant inclusion in the field of cancer biology.
Citation Format: Duaa A. Babaer, Xiaofei Wang. Activities of in vitro prepared recombinant wnt inhibitory factor-1 (Wif-1). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4604.
Abstract 4608: Survivin downregulation by α-santalol is not mediated through PI3K-Akt pathway in human breast cancer cells
Authors: BOMMAREDDY AJAY , CRISAMORE KARRYN , FILLMAN SARAH , BROZENA SARAH , STEIGERWALT JAMES , LANDIS TERRA , VANWERT ADAM L. , DWIVEDI CHANDRADHAR 
Published: July 2016

Abstract
α-Santalol, a terpenoid found in sandalwood oil, has been shown to inhibit cancer cell growth in vitro by inducing apoptosis. This study was performed to investigate the anticancer properties of α-santalol associated with the induction of apoptosis in cultured MCF-7 (estrogen receptor (ER) positive, and wild type p53) and MDA-MB-231 (ER-negative and mutant p53) breast cancer cells. Expression of major proteins examined in the study were determined using standard Western blot protocol and analyzed by LICOR-Odyssey infra-red scanner. Total protein levels of survivin were confirmed by survivin ELISA kit. Cell viability was assessed by trypan blue dye exclusion assay, and caspase-3 activity was determined by caspase-3 (active) ELISA kit. Treatment of breast cancer cells for 6 and 9 hour time intervals with α-santalol (20, 40 μM) resulted in statistically significant concentration-dependent downregulation of survivin. pAkt levels were found to be slightly upregulated despite the downregulation of survivin. Pharmacological inhibition of the PI3K-Akt pathway did not result in a synergistic/additive increase in cell death or caspase-3 activity caused by α-santalol. The study reveals that survivin downregulation by α-santalol in breast cancer cells is not mediated through the PI3K-Akt pathway.
Citation Format: AJAY BOMMAREDDY, KARRYN CRISAMORE, SARAH FILLMAN, SARAH BROZENA, JAMES STEIGERWALT, TERRA LANDIS, ADAM L. VANWERT, CHANDRADHAR DWIVEDI. Survivin downregulation by α-santalol is not mediated through PI3K-Akt pathway in human breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4608.
Abstract 461: Combined analysis of circulating epithelial cell count and serum thyroglobulin for differentiating disease status of the patients with papillary thyroid carcinoma
Authors: Tseng Ching-Ping , Lin Jen-Der , Lin Hung-Chih , Cheng Ju-Chien 
Published: July 2016

Abstract
Papillary thyroid carcinoma (PTC) is one type of thyroid cancer and accounts for about 80% of the cases. Routine surveillance by serum thyroglobulin (Tg) and medical imaging is the current practice to monitor disease progression of the patients. However, the presence of anti-Tg antibody or other influence factors may discount the value of serum Tg in disease monitoring. Whether enumeration of circulating epithelial cells (CECs) and its combined analyses with serum Tg help to define disease status of PTC patients was investigated. CECs were first enriched from the peripheral blood of the healthy control subjects (G1, n = 17) and the patients at disease-free status (G2, n = 26) or with distant metastasis (G3, n = 22). The number of CECs expressing epithelial cell adhesion molecule (EpCAM) was determined by immunofluorescence microscopy analyses. The medium number of EpCAM+-CECs was 6 (intequartile range 1-11), 12 (interquartile range 7-16) and 91 (interquartile range 31-206) cells/ml of blood for G1, G2 and G3, respectively. EpCAM+-CEC counts were significantly higher in G3 than in G1 (p&lt;0.05) and G2 (p&lt;0.05). Our data further revealed that combined analysis of serum Tg with EpCAM+-CEC defined the disease status (disease-free vs. distant metastasis) in 46 (95.8%) of the 48 patients with the AUC equivalent of 0.962 (p&lt;0.0001) in the ROC analysis. The sensitivity and specificity of the assay was 100% and 92.3%, respectively. Moreover, all 22 patients (100%) with metastatic status were defined accordingly. These data demonstrate that combined analysis of serum Tg with EpCAM+-CECs is suitable to distinguish the patients at disease-free status from the patients with distant metastasis. CEC testing thereby can supplement the current standard methods for monitoring disease status of PTC.
Citation Format: Ching-Ping Tseng, Jen-Der Lin, Hung-Chih Lin, Ju-Chien Cheng. Combined analysis of circulating epithelial cell count and serum thyroglobulin for differentiating disease status of the patients with papillary thyroid carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 461.