bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2037: Cyclin D1 overexpression supports stable EBV infection in nasopharyngeal epithelial cells
Authors: Tsao George Sai-Wah , Tsang C M. , Yip Y L. , Zhang G T. , Deng W , Lo K W. , Lau Victoria , Hau P M. , Lung M 
Published: August 2012

Abstract
Poorly or undifferentiated nasopharyngeal carcinoma (NPC) is regularly associated with Epstein-Barr virus (EBV) infection. EBV infection of premalignant nasopharyngeal epithelial cells has been postulated to play an important role in the pathogenesis of nasopharyngeal carcinoma. We have previously reported that genetic alterations could be detected in premalignant nasopharyngeal epithelial tissues. It is not clear if these genetic alterations may associate with the establishment of EBV infection. In this study, we have examined the role of cyclin D1 in supporting EBV infection in nasopharyngeal epithelial cells. While cyclin D1 is commonly expressed in nasopharyngeal carcinoma tissues we found that overexpression of cycline D1 is readily detected in dysplastic nasopharyngeal epithelial closely associated with EBV infection. Furthermore, using a panel of immortalized nasopharyngeal epithelial cells, we demonstrated that overexpression of cyclin D1 or CKD4 supports EBV infection and result in the establishment of stable EBV infected nasopharyngeal cell lines. We also observed that EBV infection induced growth inhibition and senescence in nasopharyngeal epithelial cells, which may be the underlying reason for low detection rate of EBV infection in healthy nasopharyngeal epithelial tissues. However, cyclin D1 overexpression suppressed senescence and differentiation in the immortalized nasopharyngeal epithelial cells, suggesting cyclin D1 may play an important role in supporting EBV infection in these cells. We postulated that the altered expression of cyclin D1 or CDK4 in premalignant nasopharyngeal epithelial cells may over-ride the growth suppression effects of EBV infection and support EBV latent infection in premalignant nasopharyngeal epithelial cells. Acknowledgement: This study is sponsored by grant support received from the Hong Kong Research Grant Council (Grant number: GRF780911 and AoE /M-06/08)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2037. doi:1538-7445.AM2012-2037
Abstract 2047: The interaction of ZSCAN4 with TRF1: Effects on regulation of telomere elongation in cancer cells
Authors: Lee Kyungwoo , Gollahon Lauren 
Published: August 2012

Abstract
Telomeres are repetitive sequences at the ends of chromosomes protected by DNA binding proteins of shelterin complex that form capping structures. One of these proteins, TRF1, plays a role in the regulation of telomere length through its interaction with other proteins in the shelterin complex. High levels of TRF1 expression have been shown to accelerate telomere shortening, whereas dominant-negative inhibition of TRF1 leads to telomere elongation. Recently, the newly identified Zinc finger and SCAN domain containing4 gene (ZSCAN4) plays a key role in genomic stability by regulating telomere elongation and was shown to co-localize with TRF1 foci. Here, we show that ZSCAN4 is a TRF1 association protein. We hypothesized that ZSCAN4 would affect levels of TRF1expression and correspondingly control the function of TRF1 through negative regulation and dominant-negative inhibition. Using Co-immunoprecipitation, we demonstrate that ZSCAN4 binds with TRF1 in vitro. Pull-down assay results show that ZSCAN4 directly interacts with TRF1. Using PCR mutagenesis, we have identified the binding site between ZSCAN4 and TRF1. Furthermore, over-expression of ZSCAN4 expression acts as an activator of telomere elongation. The ZSCAN4 mediated cooperative binding of TRF1 to telomeric DNA has important implications for understanding the mechanism of telomere extension.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2047. doi:1538-7445.AM2012-2047
Abstract 2050: Plk1 phosphorylation of Orc2 promotes DNA replication under conditions of stress
Authors: Song Bing , Liu X. Shawn , Davis Korbin , Liu Xiaoqi 
Published: August 2012

Abstract
Polo-like kinase 1 (Plk1) plays pivotal roles in mitosis, however, little is known about its function in S phase. In this study, we show that inhibition of Plk1 impairs DNA replication and results in slow S-phase progression in cultured cancer cells. We have identified Origin Recognition Complex 2 (Orc2), a member of the DNA replication machinery, as a Plk1 substrate and have shown that Plk1 phosphorylates Orc2 at Ser188 in vitro and in vivo. Furthermore, Orc2-S188 phosphorylation is enhanced when DNA replication is under challenge induced by UV, hydroxyurea, gemcitabine, or aphidicolin treatment; cells expressing the unphosphorylatable mutant (S188A) of Orc2 had defects in DNA synthesis under stress, suggesting that this phosphorylation event is critical to maintain DNA replication under stress. To dissect the mechanism pertinent to this observation, we showed that Orc2-S188 phosphorylation associates with DNA replication origin and that cells expressing Orc2-S188A mutant fail to maintain the functional pre-replicative complex (pre-RC) under DNA replication stress. Furthermore, the intra-S phase checkpoint is activated in Orc2-S188A-expressing cells to cause delay of S-phase progress. Our study suggests a novel role of Plk1 in facilitating DNA replication under conditions of stress to maintain genomic integrity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2050. doi:1538-7445.AM2012-2050
Abstract 2054: The BH3-only protein, Noxa, is upregulated by estrogen and promotes cell cycle progression in estrogen receptor-positive breast cancer cells
Authors: Swetzig Wendy M. , Liu Wensheng , Medisetty Rajesh , Das Gokul M. 
Published: August 2012

Abstract
According to the American Cancer Society, breast cancer is the second leading cause of cancer-related deaths in American women, with more than 200,000 new cases diagnosed annually. In addition, the vast majority of breast cancers are initially hormone-dependent and 70% are estrogen receptor (ER)-positive (Colditz, J. Natl. Cancer Inst., 1998; Hankinson et al., Breast Cancer Res., 2004; and Harvey et al., J. Clin. Oncol., 1999), highlighting the importance of estrogen signaling pathways in breast oncogenesis. It has been well-established that estrogen/17β-estradiol/E2 stimulates cell growth and inhibits apoptosis in ER-positive breast cancer cells; however, recent reports have demonstrated that E2 paradoxically induces the expression of Noxa/PMAIP1, a BH3-only pro-apoptotic member of the Bcl-2 family. In the present study, we report on the mechanisms by which E2 upregulates Noxa expression and the associated cellular effects on apoptosis and cell cycle progression in ER-positive MCF7 human breast cancer cells. We demonstrate that c-Myc, ERα, and E2F1 are involved in the transcriptional upregulation of Noxa following E2 treatment. Specific knockdown of c-Myc and ERα protein expression using siRNA technology inhibited E2-mediated induction of Noxa expression. Furthermore, E2 also promoted the recruitment of c-Myc and ERα to the NOXA promoter in chromatin immunoprecipitation (ChIP) assays, suggesting that these two proteins are indeed mediators of Noxa upregulation following E2 treatment. Although p53 is an important regulator of Noxa transcription under conditions of cellular stress, our data demonstrate that E2-mediated upregulation of Noxa is a p53-independent process, as knocking down p53 with specific siRNA did not block E2-mediated induction of Noxa. Consistent with this result, E2 treatment failed to induce the recruitment of p53 to the NOXA promoter in ChIP assays. Interestingly, E2-mediated upregulation of Noxa was associated with cell cycle progression but not with apoptosis under normal, unstressed cellular conditions. Cell cycle analysis by flow cytometry showed that siRNA-mediated knockdown of Noxa caused cell cycle arrest in G0/G1-phase and significantly delayed the G1-to-S-phase transition following E2 treatment. Collectively, these data indicate that Noxa expression is required for cell cycle progression in ER-positive breast cancer cells, suggesting a novel role for the BH3-only protein Noxa, outside of its traditional role as an apoptosis sensitizer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2054. doi:1538-7445.AM2012-2054
Abstract 2055: p21CIP1 mediates reciprocal switching between invasion and proliferation during metastasis
Authors: Hazan Rachel 
Published: August 2012

Abstract
Cell proliferation and invasion are critical for malignant progression, yet how these processes relate to each other and whether they regulate one another during metastasis is unknown. We show that invasiveness of breast cancer cells is associated with growth arrest due to p21CIP1 upregulation. Knockdown of p21CIP1 increases proliferation and suppresses invasion. Since p21CIP1 acts to inhibit Cyclin E during cell cycle progression, we demonstrated that a constitutively active form of Cyclin E had similar effects to p21CIP1 inhibition resulting in increased proliferation and suppressed invasion. We tested these findings in vivo in the Polyoma middle T mammary tumor model in which p21CIP1 was deleted. p21CIP1 knockout mice exhibited dramatic suppression of metastasis, independent of tumor growth. Metastasis suppression was associated with striking cytoskeletal reorganization leading to a shift from stress fibers to cortical actin, tightening of cell junctions, and cytokeratin upregulation. Thus, P21CIP1 regulates metastasis by mediating dynamic switching between invasion and proliferation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2055. doi:1538-7445.AM2012-2055
Abstract 2062: Peptidylprolyl cis/trans isomerase A1 (Pin1) is modified by lipid electrophiles generated during oxidative stress
Authors: Aluise Christopher D. , Marnett Lawrence J. 
Published: August 2012

Abstract
Oxidation of membrane phospholipids is associated with inflammation and cancer. Phospholipid peroxidation results in the production of reactive electrophiles that adduct proteins and modulate their function. 4-Hydroxynonenal (HNE), a common product of oxidative damage to lipids, adducts proteins at exposed Cys, His, or Lys residues. Here, we provide evidence that peptidyl-prolyl cis/trans isomerase A1 (Pin1), an enzyme that catalyzes the conversion of pSer/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE-modification. Incubation of purified Pin1 with HNE followed by MALDI-TOF/TOF mass spectrometry revealed that the most reactive amino acids are His-157 and Cys-113, both of which are active site residues. Pin1 was adducted in MDA-MB-231 breast cancer cells treated with 8-alkynyl-HNE as judged by click chemistry conjugation with biotin followed by streptavidin-based pulldown and western blotting with anti-Pin1 antibody. siRNA knockdown of Pin1 in MDA-MB-231 cells partially protected the cells from HNE-induced toxicity. Recent studies indicate that Pin1 is an important molecular target for the chemopreventive effects of green tea polyphenols. The present study establishes that it is also a target for electrophilic modification by products of lipid peroxidation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2062. doi:1538-7445.AM2012-2062
Abstract 2065: Loss of Nrf2 increases susceptibility to radiation induced bone loss
Authors: Rana Tapasi , Schultz MIchelle , Freeman MIchael , Biswas Swati 
Published: August 2012

Abstract
A fundamental clinical complication in the treatment of patients with metastatic breast cancer is severe bone loss. Patients with breast cancer routinely received both chemotherapy and radiotherapy, both are known to increase oxidative stress and bone loss. Underlying mechanism of cancer therapy induced bone loss is poorly understood. We have previouslyreported that treatment with radiation (RT) increases TGFβ1 levels in mice. TGFβ1 increases oxidative stress by induction of reactive oxygen species (ROS). TGFβ1 increases oxidative stress by induction of reactive oxygen species (ROS). TGFβ1/Smad3 signaling suppresses Nrf2 (Nuclear factor erythroid-derived 2), a master transcription factor that positively regulates induction of antioxidant gene expression resulting in elevated ROS levels. Our objective is to test the hypothesis whether loss of Nrf2 gene increases the radiation induced bone loss. We have used age matched wild type control and Nrf2-/- mice. Mice were irradiated (single dose, 20 Gy) on the hind legs and microCT analysis was done to measure the overall bone loss. A similar increase in bone loss was noted in mice following histological analysis of the long bones. Additionally, reduction in osteoblast colony forming units and osteoblast differentiation were also noted. We have seen a higher number of osteoclasts in Nrf2-/- mice compared to wild type control and following radiation, the trend remains same. We conclude that, loss of Nrf2 leads to incraesed susceptibility to the radiation induced bone damage.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2065. doi:1538-7445.AM2012-2065
Abstract 2068: Opposite effects of arsenic trioxide on the Nrf2 pathway in oral squamous cell carcinoma in vitro and in vivo
Authors: Zhang Xinyan , Su Ying , Zhang Min 
Published: August 2012

Abstract
Nuclear factor erythroid derived like 2 (Nrf2) is a critical transcriptional factor in mediating cellular defense mechanisms against oxidative stress or electrophiles. Arsenic has been reported to induce malignant transformation of human cells through Nrf2-dependent signaling pathway. However, arsenic is also a promising cancer therapeutic drug for solid tumors, including oral squamous cell carcinoma (OSCC). It is still unclear how Nrf2 may mediate cellular response of OSCC cells when treated with arsenic. In order to fully understand the impact of Nrf2 signaling in human OSCC, we examined expression of Nrf2 and Nrf2-regulated genes in arsenic trioxide (ATO) treated OSCC cells in vitro and in ATO-treated OSCC xenografts. ATO exerted its anti-tumor effects on both cultured OSCC cells and OSCC xenografts by inhibiting cell growth, suppressing angiogenesis and inducing apoptosis. ATO activated a silent Nrf2 pathway in cultured OSCC cells as shown by induction of Nrf2 and Nrf2-regulated genes, NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), in a dose-dependent manner. On the contrary, Nrf2 pathway became active in OSCC xenograft tumors, and ATO treatment down-regulated expression of Nrf2 and Nrf2-regulated genes. Our study clearly demonstrated opposite effects of ATO on Nrf2 pathway in OSCC in vitro and in vivo.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2068. doi:1538-7445.AM2012-2068
Abstract 2071: Docosahexaenoic acid-induced apoptosis is directly linked to mitochondria-mediated reactive oxygen species production in human cervical cancer cells
Authors: Jing Kaipeng , Shin Soyeon , Kim Nayeong , Jeong Soyeon , Oh Hye-Rim , Cho Eun-Ah , Park Ji-Hoon , Seo Kang-Sik , Heo Jun-Young , Han Jeong-Su , Park Jong-Il , Kweon Gi-Ryang , Park Seung-Kiel , Yoon Wan-Hee , Hwang Byung-Doo , Lim Kyu 
Published: August 2012

Abstract
Reactive oxygen species (ROS) produced by docosahexaenoic acid (DHA) have an important function in cancer cell death. However, the exact mechanism of ROS production, after DHA stimulation, is not clearly understood. Here, we determined that elevated levels of ROS generated by mitochondrial respiration is directly associated with DHA-induced cervical cancer cell death. The levels of caspase 3 activity, TUNEL-positive staining cells and Sub-G1 portion were markedly increased in DHA-treated cancer cells, suggesting that apoptosis is responsible for the DHA-induced cervical cancer cell death. Furthermore, DHA was able to induce both mitochondrial complex I substrate- and complex II substrate-supported mitochondrial ROS production in isolated mitochondria from rodent liver. Meanwhile, a reduction in oxygen consumption rate and an increase in mitochondrial ROS production as measured by MitoSOX, were also observed in DHA-treated cancer cells, indicating that DHA can directly act on mitochondrial respiration and enhance ROS generation. The role of DHA-induced mitochondrial ROS production in apoptosis was further identified by the findings that DHA reduced the mitochondrial membrane potential, resulting in cardiolipin oxidation and cytochrome c release from mitochondria, and that N-acetylcysteine, an antioxidant almost completely blocked these processes as well as ROS production occurred in mitochondria and remarkably reversed the apoptotic cell death triggered by DHA. From the results presented here, we conclude that mitochondria actively participate in the DHA-induced apoptotic cell death by the generation of mitochondrial ROS. (This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (2011-0006232 and 2011-0003060)).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2071. doi:1538-7445.AM2012-2071
Abstract 2073: Parthenolide-mediated redox modification of Keap1 leads to differential effects on radiosensitivities of prostate cancer and normal cells
Authors: Xu Yong , Fang Fang , Clair Daret K. St. , Sun Yulan , Clair William H. St. 
Published: August 2012

Abstract
Elevated oxidative stress is more frequently observed in cancer cells than in normal cells. Thus, further exposure to exogenous reactive oxygen species (ROS) is expected to push cancer to cell death, whereas normal cells may maintain redox homeostasis through ROS mediated adaptive responses. We previously demonstrated that parthenolide selectively enhances radiosensitivity of prostate cancer cells through activation of a NADPH oxidase-dependent redox signaling pathway. Our present study identifies the status of the redox sensitive Kelch-like ECH-associated protein-1 (Keap1) as a central regulator responsible for the parthenolide-mediated differential redox modification. This results in both a radiosensitization effect in prostate cancer cells and a radioresistance effect in normal prostate epithelial cells. Mechanistically, parthenolide increases the reduced state of Keap1 in prostate cancer cells in a thioredoxin-dependent manner but causes oxidation of Keap1 in normal prostate epithelial cells. Selective knock-down of thioredoxin leads to Keap1 oxidation and subsequent activation of the NF-E2-related factor 2 (Nrf2). These results suggest that redox modification of Keap1 is a major mechanism for the parthenolide effect on radiation therapy in cancer and normal cells. Consistent with the differential effect of parthenolide in cancer and normal cells, the levels of superoxide, hydrogen peroxide and peroxynitrite were selectively increased in parthenolide treated prostate cancer cells but not in normal prostate epithelial cells, indicating the selective increase of ROS in cancer cells. Parthenolide reduces the levels of Nrf2 targets, antioxidant proteins including manganese superoxide dismutase and heme oxygenase in prostate cancer cells, but increases the levels of these proteins in normal cells. This suggests that an antioxidant response is critical for the protection of normal cells against ROS generated from parthenolide.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2073. doi:1538-7445.AM2012-2073