bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ribosome Biogenesis and the Translation Process inEscherichia coli
Authors: Kaczanowska Magdalena , Rydén-Aulin Monica 
Published: September 2007

SUMMARYTranslation, the decoding of mRNA into protein, is the third and final element of the central dogma. The ribosome, a nucleoprotein particle, is responsible and essential for this process. The bacterial ribosome consists of three rRNA molecules and approximately 55 proteins, components that are put together in an intricate and tightly regulated way. When finally matured, the quality of the particle, as well as the amount of active ribosomes, must be checked. The focus of this review is ribosome biogenesis inEscherichia coliand its cross-talk with the ongoing protein synthesis. We discuss how the ribosomal components are produced and how their synthesis is regulated according to growth rate and the nutritional contents of the medium. We also present the many accessory factors important for the correct assembly process, the list of which has grown substantially during the last few years, even though the precise mechanisms and roles of most of the proteins are not understood.
THE QUALITATIVE TREATMENT OF SPATIAL DATA
Authors: TAKAHASHI KAZUKO , SUMITOMO TAKAO 
Published: September 2007

This paper aims at an efficient treatment of spatial data using qualitative representation. We propose a new framework called PLCA, which provides a symbolic representation for the figure in a two-dimensional plane, focusing on the connections between regions. It is based on four simple objects: points(P), lines(L), circuits(C) and areas(A). The entire figure is represented as a combination of these objects. Pairs of areas, circuits or lines never cross. The simple, clear data structure based on objects makes the system feasible and easy to implement. A PLCA expression can be subject to topological reasoning such as judging the connection patterns of areas. We define the operations of area integration and area division on a PLCA expression. These operations preserve the consistency of the expression, and correspond to real actions on the figures. We can add attributes to each object, such as the properties that hold on an area or that an object represents, and make an attributed PLCA. The operations of area integration/division on an attributed PLCA correspond to the alteration of the classification level of objects, and semantic spatial reasoning can be performed on an attributed PLCA.
Fixed Points and Hyers-Ulam-Rassias Stability of Cauchy-Jensen Functional Equations in Banach Algebras
Authors: Park Choonkil 
Published: September 2007

AbstractWe prove the Hyers-Ulam-Rassias stability of homomorphisms in real Banach algebras and of generalized derivations on real Banach algebras for the following Cauchy-Jensen functional equations: "Equation missing", "Equation missing", which were introduced and investigated by Baak (2006). The concept of Hyers-Ulam-Rassias stability originated from Th. M. Rassias' stability theorem that appeared in his paper (1978).
Activation of Insulin-like Growth Factor Signaling Induces Apoptotic Cell Death Under Prolonged Hypoxia by Enhancing Endoplasmic Reticulum Stress Response
Authors: Endo Hiroko , Murata Kohei , Mukai Mutsuko , Ishikawa Osamu , Inoue Masahiro 
Published: September 2007

Abstract
Malignant cells in solid tumors survive under prolonged hypoxia and can be a source of resistance to current cancer therapies. Mammalian target of rapamycin (mTOR), one of the downstream molecules of the insulin-like growth factor (IGF) pathway, is a key regulator of translation, integrating multiple environmental and nutritional cues. The activity of mTOR is known to be suppressed under hypoxic conditions in cancer cells, whereas the contribution of this suppression to cell survival has not yet been clarified. We show that stimulating IGF signaling provoked caspase-dependent apoptosis under low oxygen tension in two cancer cell lines, COLO 320 and AsPC-1. In concurrence with increased levels of BAD phosphorylation, cell death was not accompanied by cytochrome c release from mitochondria. The cells were rescued from apoptosis when phosphatidylinositol 3-kinase (PI3K) or mTOR activity was inhibited, suggesting that these signals are critical in the observed cell death. IGFs and insulin enhanced the endoplasmic reticulum (ER) stress response as monitored by induction of the CCAAT/enhancer binding protein homologous protein (CHOP) proteins and the X box protein-1 splicing under hypoxic conditions, and this response was suppressed by inhibiting PI3K and mTOR activity. IGF-induced cell death under hypoxic conditions was prevented by treatment with cycloheximide, suggesting that de novo protein synthesis is required. Indeed, suppression of CHOP protein levels with small hairpin RNA reduced cell death. Taken together, the data suggest that stimulating IGF signaling under hypoxic conditions provokes apoptosis by enhancing the ER stress response. [Cancer Res 2007;67(17):8095–103]
Human Thyroid Tumor Cell Lines Derived from Different Tumor Types Present a Common Dedifferentiated Phenotype
Authors: van Staveren Wilma C.G. , Solís David Weiss , Delys Laurent , Duprez Laurence , Andry Guy , Franc Brigitte , Thomas Gerry , Libert Frédérick , Dumont Jacques E. , Detours Vincent , Maenhaut Carine 
Published: September 2007

AbstractCell lines are crucial to elucidate mechanisms of tumorigenesis and serve as tools for cancer treatment screenings. Therefore, careful validation of whether these models have conserved properties of in vivo tumors is highly important. Thyrocyte-derived tumors are very interesting for cancer biology studies because from one cell type, at least five histologically characterized different benign and malignant tumor types can arise. To investigate whether thyroid tumor–derived cell lines are representative in vitro models, characteristics of eight of those cell lines were investigated with microarrays, differentiation markers, and karyotyping. Our results indicate that these cell lines derived from differentiated and undifferentiated tumor types have evolved in vitro into similar phenotypes with gene expression profiles the closest to in vivo undifferentiated tumors. Accordingly, the absence of expression of most thyrocyte-specific genes, the nonresponsiveness to thyrotropin, as well as their large number of chromosomal abnormalities, suggest that these cell lines have acquired characteristics of fully dedifferentiated cells. They represent the outcome of an adaptation and evolution in vitro, which questions the reliability of these cell lines as models for differentiated tumors. However, they may represent useful models for undifferentiated cancers, and by their comparison with differentiated cells, can help to define the genes involved in the differentiation/dedifferentiation process. The use of any cell line as a model for a cancer therefore requires prior careful and thorough validation for the investigated property. [Cancer Res 2007;67(17):8113–20]
Insulin-Like Growth Factor-I, Regulating Aromatase Expression through Steroidogenic Factor 1, Supports Estrogen-Dependent Tumor Leydig Cell Proliferation
Authors: Sirianni Rosa , Chimento Adele , Malivindi Rocco , Mazzitelli Ignazio , Andò Sebastiano , Pezzi Vincenzo 
Published: September 2007

Abstract
The aim of this study was to investigate the role of estrogens in Leydig cell tumor proliferation. We used R2C rat Leydig tumor cells and testicular samples from Fischer rats with a developed Leydig tumor. Both experimental models express high levels of aromatase and estrogen receptor α (ERα). Treatment with exogenous 17β-estradiol (E2) induced proliferation of R2C cells and up-regulation of cell cycle regulators cyclin D1 and cyclin E, the expression of which was blocked by addition of antiestrogens. These observations led us to hypothesize an E2/ERα–dependent mechanism for Leydig cell tumor proliferation. In determining the molecular mechanism responsible for aromatase overexpression, we found that total and phosphorylated levels of transcription factors cyclic AMP–responsive element binding protein and steroidogenic factor 1 (SF-1) were higher in tumor samples. Moreover, we found that tumor Leydig cells produce high levels of insulin-like growth factor I (IGF-I), which increased aromatase mRNA, protein, and activity as a consequence of increased total and phosphorylated SF-1 levels. Specific inhibitors of IGF-I receptor, protein kinase C, and phosphatidylinositol 3-kinase determined a reduction in SF-1 expression and in IGF-I–dependent SF-1 recruitment to the aromatase PII promoter. The same inhibitors also inhibited aromatase expression and activity and, consequently, R2C cell proliferation. We can conclude that one of the molecular mechanisms determining Leydig cell tumorigenesis is an excessive estrogen production that stimulates a short autocrine loop determining cell proliferation. In addition, cell-produced IGF-I amplifies estrogen signaling through an SF-1–dependent up-regulation of aromatase expression. The identification of this molecular mechanism will be helpful in defining new therapeutic approaches for Leydig cell tumors. [Cancer Res 2007;67(17):8368–77]
In vivo Role of NAD(P)H:Quinone Oxidoreductase 1 in Metabolic Activation of Mitomycin C and Bone Marrow Cytotoxicity
Authors: Adikesavan Anbu Karani , Barrios Roberto , Jaiswal Anil K. 
Published: September 2007

Abstract
NAD(P)H:quinone oxidoreductase 1−/− (NQO1−/−), NQO1+/− along with NRH:quinone oxidoreductase 2−/− (NQO2−/−), and wild-type (WT) mice were exposed to five once weekly doses of mitomycin C. The mice were euthanized 15 weeks after the first dose. Blood cell counts and histologic analyses were done. WT and NQO2−/− mice showed hypocellularity and a significant increase in adipocytes in bone marrow. They also showed anemia because of the loss of RBC and hemoglobin. The neutrophils and platelets were reduced, whereas other blood cell types and tissues were normal. Interestingly, NQO1−/− mice showed a complete resistance to mitomycin C–induced bone marrow cytotoxicity and reduction in RBC, hemoglobin, and neutrophils. NQO1+/− mice also showed limited resistance to mitomycin C–induced bone marrow cytotoxicity. These data show a major in vivo role of NQO1 in metabolic activation of mitomycin C with implications in mitomycin C chemotherapy. [Cancer Res 2007;67(17):7966–71]
Enrichment of a Population of Mammary Gland Cells that Form Mammospheres and Have In vivo Repopulating Activity
Authors: Liao Mai-Jing , Zhang Cheng Cheng , Zhou Beiyan , Zimonjic Drazen B. , Mani Sendurai A. , Kaba Megan , Gifford Ann , Reinhardt Ferenc , Popescu Nicholas C. , Guo Wenjun , Eaton Elinor Ng , Lodish Harvey F. , Weinberg Robert A. 
Published: September 2007

Abstract
The identification of mammary gland stem cells (MGSC) or progenitors is important for the study of normal breast development and tumorigenesis. Based on their immunophenotype, we have isolated a population of mouse mammary gland cells that are capable of forming “mammospheres” in vitro. Importantly, mammospheres are enriched for cells that regenerate an entire mammary gland on implantation into a mammary fat pad. We also undertook cytogenetic analyses of mammosphere-forming cells after prolonged culture, which provided preliminary insight into the genomic stability of these cells. Our identification of new cell surface markers for enriching mammosphere-initiating cells, including endoglin and prion protein, will facilitate the elucidation of the cell biology of MGSC. [Cancer Res 2007;67(17):8131–8]
Lipid Raft–Specific Knockdown of Src Family Kinase Activity Inhibits Cell Adhesion and Cell Cycle Progression of Breast Cancer Cells
Authors: Hitosugi Taro , Sato Moritoshi , Sasaki Kazuki , Umezawa Yoshio 
Published: September 2007

Abstract
Src family kinase (SFK) is known to control various cell functions, but the significance of the location of its activation was largely unknown. We herein revealed that SFK activation occurs in lipid rafts. Based on this finding, we have developed a lipid raft–targeted SFK inhibitory fusion protein (LRT-SIFP) that inhibits the SFK activity in lipid rafts. LRT-SIFP has a peptide inhibitor of SFK and a lipid raft–targeting sequence in which two cysteine residues are palmitoylated for clustering in lipid rafts. LRT-SIFP was found to inhibit cell adhesion and cell cycle progression of human breast cancer cell lines MCF-7 and MDA-MB231. On the other hand, the cell functions of MCF-7 cells were found to be not affected with a previously developed peptide inhibitor of SFK that lacks the lipid raft–targeting sequence. In addition, when we replaced the targeting sequence of LRT-SIFP with the consensus sequence for geranylgeranylation to make LRT-SIFP unable to cluster in lipid rafts, this mutated LRT-SIFP did not show any effect on the above cell functions of MCF-7 cells. Furthermore, in contrast to the breast cancer cell lines, LRT-SIFP did not show any inhibitory effect on cell adhesion and cell cycle progression of human normal cell line HEK293. The present lipid raft–specific knockdown of SFK activity would potentially be useful for selective cancer therapy to prevent tumorigenesis and metastasis of breast cancer cells. [Cancer Res 2007;67(17):8139–48]
Ribosomal S6 Kinase 2 Is a Key Regulator in Tumor Promoter–Induced Cell Transformation
Authors: Cho Yong-Yeon , Yao Ke , Kim Hong-Gyum , Kang Bong Seok , Zheng Duo , Bode Ann M. , Dong Zigang 
Published: September 2007

AbstractThe ribosomal S6 kinase 2 (RSK2), a member of the p90RSK (RSK) family of proteins, is a widely expressed serine/threonine kinase that is activated by extracellular signal-regulated kinase 1/2 and phosphoinositide-dependent kinase 1 in response to many growth factors and peptide hormones. Its activation signaling enhances cell survival. However, the roles of RSK2 in cell transformation have not yet been elucidated. Here, we found that RSK2 is a critical serine/threonine kinase for the regulation of cell transformation. When cells were stimulated with tumor promoters, such as epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylation of RSK was increased within 5 min. Cell proliferation was suppressed in RSK2−/− mouse embryonic fibroblasts (MEFs) compared with RSK2+/+ MEFs. Moreover, RSK2−/− MEFs accumulated at the G1 phase of the cell cycle under normal cell culture conditions as well as after stimulation with EGF or TPA. In the anchorage-independent cell transformation assay (soft agar), stable expression of RSK2 in JB6 cells significantly enhanced colony formation in either the presence or absence of tumor promoters. Furthermore, knockdown of RSK2 with small interfering RNA-RSK2 suppressed constitutively active Ras (RasG12V)-induced foci formation in NIH3T3 cells. In addition, kaempferol, an inhibitor of RSK2, suppressed EGF-induced colony formation of JB6 Cl41 cells in soft agar, which was associated with inhibition of histone H3 phosphorylation (Ser10). These results showed that RSK2 is a key regulator for cell transformation induced by tumor promoters such as EGF and TPA. [Cancer Res 2007;67(17):8104–12]
Taxol Increases the Amount and T Cell–Activating Ability of Self-Immune Stimulatory Multimolecular Complexes Found in Ovarian Cancer Cells
Authors: Tsuda Naotake , Chang David Z. , Mine Takashi , Efferson Clay , García-Sastre Adolfo , Wang Xinhui , Ferrone Soldano , Ioannides Constantin G. 
Published: September 2007

Abstract
It has been proposed that chemotherapy enhances tumor antigen (TA)–specific immunity. The molecular form of TA from ovarian tumor that activates cellular immunity is unknown. We report here identification of a novel molecular form of immunogenic TA for CD8+ cells named self-immune stimulatory multimolecular complexes (ISMMC). ISMMC consist of a molecular complex of polyosome/ribosome-bound ubiquitinated nascent HER-2 polypeptides. This complex is chaperoned by heat shock protein Gp96, which mediates ISMMC uptake by antigen-presenting cells through the scavenger receptor CD91. RNAs in ISMMC stimulate immature dendritic cells to secrete interleukin 12 and induce IFN-γ in peripheral blood mononuclear cells. ISMMC dissociate, retrotranslocate from the lysosome to cytoplasm, and are processed to peptides by the proteasome. At subpharmacologic doses, Taxol increased the amount of ISMMC by three to four times and modified their composition by inducing the attachment of cochaperones of HSP70, such as the mitotic-phase phosphoprotein 11J. On a total protein basis, Taxol induced ISMMC, expanded more CD8+ cells, activated more CD56+ NKG2D+ cells to produce IFN-γ, and were more potent inducers of high T-cell receptor density Perforin+ cells than native ISMMC and peptide E75. Elucidation of the composition of ISMMC and identification of adducts formed by Taxol should be important for developing molecular cancer vaccines. [Cancer Res 2007;67(17):8378–87]
Silibinin Sensitizes Human Glioma Cells to TRAIL-Mediated Apoptosis via DR5 Up-regulation and Down-regulation of c-FLIP and Survivin
Authors: Son Yong-gyu , Kim Eun Hee , Kim Jin Yeop , Kim Seung U. , Kwon Taeg Kyu , Yoon A-Rum , Yun Chae-Ok , Choi Kyeong Sook 
Published: September 2007

Abstract
Silibinin, a flavonoid isolated from Silybum marianum, has been reported to have cancer chemopreventive and therapeutic effects. Here, we show that treatment with subtoxic doses of silibinin in combination with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant glioma cells, but not in human astrocytes, suggesting that this combined treatment may offer an attractive strategy for safely treating gliomas. Although the proteolytic processing of procaspase-3 by TRAIL was partially blocked in glioma cells, cotreatment with silibinin efficiently recovered TRAIL-induced caspase activation in these cells. Silibinin treatment up-regulated DR5, a death receptor of TRAIL, in a transcription factor CHOP-dependent manner. Furthermore, treatment with silibinin down-regulated the protein levels of the antiapoptotic proteins FLIPL, FLIPS, and survivin through proteasome-mediated degradation. Taken together, our results show that the activity of silibinin to modulate multiple components in the death receptor–mediated apoptotic pathway is responsible for its ability to recover TRAIL sensitivity in TRAIL-resistant glioma cells. [Cancer Res 2007;67(17):8274–84]
Tissue-Specific Consequences of Cyclin D1 Overexpression in Prostate Cancer Progression
Authors: He Yue , Franco Omar E. , Jiang Ming , Williams Karin , Love Harold D. , Coleman Ilsa M. , Nelson Peter S. , Hayward Simon W. 
Published: September 2007

AbstractThe cyclin D1 oncogene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the Rb protein and promotes progression through G1 to S phase of the cell cycle. Several prostate cancer cell lines and a subset of primary prostate cancer samples have increased cyclin D1 protein expression. However, the relationship between cyclin D1 expression and prostate tumor progression has yet to be clearly characterized. This study examined the effects of manipulating cyclin D1 expression in either human prostatic epithelial or stromal cells using a tissue recombination model. The data showed that overexpression of cyclin D1 in the initiated BPH-1 cell line increased cell proliferation rate but did not elicit tumorigenicity in vivo. However, overexpression of cyclin D1 in normal prostate fibroblasts (NPF) that were subsequently recombined with BPH-1 did induce malignant transformation of the epithelial cells. The present study also showed that recombination of BPH-1 + cyclin D1–overexpressing fibroblasts (NPFcyclin D1) resulted in permanent malignant transformation of epithelial cells (BPH-1NPF-cyclin D1 cells) similar to that seen with carcinoma-associated fibroblasts (CAF). Microarray analysis showed that the expression profiles between CAFs and NPFcyclin D1 cells were highly concordant including cyclin D1 up-regulation. These data indicated that the tumor-promoting activity of cyclin D1 may be tissue specific. [Cancer Res 2007;67(17):8188–97]
Epidermal Growth Factor Receptor (EGFR) Ubiquitination as a Mechanism of Acquired Resistance Escaping Treatment by the Anti-EGFR Monoclonal Antibody Cetuximab
Authors: Lu Yang , Li Xinqun , Liang Ke , Luwor Rodney , Siddik Zahid H. , Mills Gordon B. , Mendelsohn John , Fan Zhen 
Published: September 2007

Abstract
Cetuximab is an epidermal growth factor receptor (EGFR)–blocking antibody that has been approved for treatment of patients with metastatic colorectal cancer. In this study, we investigated biochemical changes in signaling pathways of a cetuximab-resistant subline of DiFi colorectal cancer cells (DiFi5) that was developed by exposing the parental sensitive cells to subeffective doses of cetuximab over an extended period of time. Compared with parental DiFi cells that express high levels of EGFR and in which cetuximab induces apoptosis, the cetuximab-resistant DiFi5 cells showed markedly lower protein levels of EGFR, an increased association of EGFR with Cbl, and an increased ubiquitination of EGFR. DiFi5 cells also had a markedly higher level of Src-Y416 phosphorylation both at baseline and on EGF stimulation. Although EGFR levels were low, DiFi5 cells responded to EGF stimulation with robust phosphorylation of EGFR on Y845 and strong phosphorylation of Akt and extracellular signal–regulated kinase, comparable to those of parental cells. Most importantly, inhibition of Src kinase activity with PP2 reversed the resistance of DiFi5 cells to cetuximab-induced apoptosis without affecting the levels of EGFR in the cells. Our results indicate that colorectal cancer cells may develop acquired resistance to cetuximab via altering EGFR levels through promotion of EGFR ubiquitination and degradation and using Src kinase-mediated cell signaling to bypass their dependency on EGFR for cell growth and survival. [Cancer Res 2007;67(17):8240–7]
Activity of Androgen Receptor Antagonist Bicalutamide in Prostate Cancer Cells Is Independent of NCoR and SMRT Corepressors
Authors: Hodgson Myles C. , Astapova Inna , Hollenberg Anthony N. , Balk Steven P. 
Published: September 2007

Abstract
The mechanisms by which androgen receptor (AR) antagonists inhibit AR activity, and how their antagonist activity may be abrogated in prostate cancer that progresses after androgen deprivation therapy, are not clear. Recent studies show that AR antagonists (including the clinically used drug bicalutamide) can enhance AR recruitment of corepressor proteins [nuclear receptor corepressor (NCoR) and silencing mediator of retinoid and thyroid receptors (SMRT)] and that loss of corepressors may enhance agonist activity and be a mechanism of antagonist failure. We first show that the agonist activities of weak androgens and an AR antagonist (cyproterone acetate) are still dependent on the AR NH2/COOH-terminal interaction and are enhanced by steroid receptor coactivator (SRC)-1, whereas the bicalutamide-liganded AR did not undergo a detectable NH2/COOH-terminal interaction and was not coactivated by SRC-1. However, both the isolated AR NH2 terminus and the bicalutamide-liganded AR could interact with the SRC-1 glutamine-rich domain that mediates AR NH2-terminal binding. To determine whether bicalutamide agonist activity was being suppressed by NCoR recruitment, we used small interfering RNA to deplete NCoR in CV1 cells and both NCoR and SMRT in LNCaP prostate cancer cells. Depletion of these corepressors enhanced dihydrotestosterone-stimulated AR activity on a reporter gene and on the endogenous AR-regulated PSA gene in LNCaP cells but did not reveal any detectable bicalutamide agonist activity. Taken together, these results indicate that bicalutamide lacks agonist activity and functions as an AR antagonist due to ineffective recruitment of coactivator proteins and that enhanced coactivator recruitment, rather than loss of corepressors, may be a mechanism contributing to bicalutamide resistance. [Cancer Res 2007;67(17):8388–95]