bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cpx Signal Transduction Is Influenced by a Conserved N-Terminal Domain in the Novel Inhibitor CpxP and the Periplasmic Protease DegP
Authors: Buelow Daelynn R. , Raivio Tracy L. 
Published: September 2005

ABSTRACT

In
Escherichia coli
, envelope stress can be overcome by three different envelope stress responses: the σ
E
stress response and the Bae and Cpx two-component systems. The Cpx envelope stress response is controlled by the sensor kinase CpxA, the response regulator CpxR, and the novel periplasmic protein CpxP. CpxP mediates feedback inhibition of the Cpx pathway through a hypothetical interaction with the sensing domain of CpxA. No informative homologues of CpxP are known, and thus it is unclear how CpxP exerts this inhibition. Here, we identified six
cpxP
loss-of-function mutations using a CpxP-β-lactamase (CpxP′-′Bla) translational fusion construct. These loss-of-function mutations identified a highly conserved, predicted α-helix in the N-terminal domain of CpxP that affects both the function and the stability of the protein. In the course of this study, we also found that CpxP′-′Bla stability is differentially controlled by the periplasmic protease DegP in response to inducing cues and that mutation of
degP
diminishes Cpx pathway activity. We propose that the N-terminal α-helix is an important functional domain for inhibition of the Cpx pathway and that CpxP is subject to DegP-dependent proteolysis.
Tn5386, a Novel Tn916-Like Mobile Element inEnterococcus faeciumD344R That Interacts with Tn916To Yield a Large Genomic Deletion
Authors: Rice Louis B. , Carias Lenore L. , Marshall Steven , Rudin Susan D. , Hutton-Thomas Rebecca 
Published: September 2005

ABSTRACTWe describe Tn5386, a novel ca.-29-kb Tn916-like mobile element discovered to occur in ampicillin-resistant, Tn916-containingEnterococcus faeciumD344R. PCR amplification experiments after overnight growth with or without tetracycline revealed “joint” regions of circularized Tn5386composed of 6-bp sequences linking different transposon termini. In one case (no tetracycline), the termini were consistent with those derived by target site analysis of the integrated element. In the other case, the termini were virtually identical in distance from the integrase binding regions, as seen with Tn916. These data are consistent with a model in which one PCR product results from the action of Tn5386integrase, whereas the other results from the action of the Tn916integrase on Tn5386. Spontaneous conversion of D344R to an ampicillin-susceptible phenotype (D344SRF) was associated with a 178-kb deletion extending from the left end of Tn5386to the left end of Tn916. Examination of the Tn5386junction after the large deletion event suggests that the deletion resulted from an interaction between the nonintegrase ends of Tn5386and Tn916. The terminus of Tn5386identified in this reaction suggested that it may have resulted from the activity of the Tn916integrase (IntTn916). The “joint” of the circular element resulting from this excision was amplifiable from D344R, the sequence of which revealed a heteroduplex consistent with IntTn916-mediated excision. In contrast, Tn5386joints amplified from ampicillin-susceptible D344SRF revealed ends consistent with Tn5386integrase activity, reflecting the absence of Tn916from this strain. Tn5386represents a new member of the Tn916transposon family. Our data suggest that excision of Tn5386can be catalyzed by the Tn916integrase and that large genomic deletions may result from the interaction between these heterologous elements.
Inactivation of Protein Translocation by Cold-Sensitive Mutations in the
yajC
-
secDF
Operon
Authors: Nouwen Nico , Driessen Arnold J. M. 
Published: September 2005

ABSTRACT

Most mutations in the
yajC
-
secDF
operon identified via genetic screens confer a cold-sensitive growth phenotype. Here we report that two of these mutations confer this cold-sensitive phenotype by inactivating the SecDF-YajC complex in protein translocation.
ENTANGLED MARKOV CHAINS GENERATED BY SYMMETRIC CHANNELS
Authors: MIYADERA TAKAYUKI 
Published: September 2005

A notion of entangled Markov chain was introduced by Accardi and Fidaleo in the context of quantum random walk. They proved that, in the finite-dimensional case, the corresponding states have vanishing entropy density, but they did not prove that they are entangled. In this note this entropy result is extended to the infinite-dimensional case under the assumption of finite speed of hopping. Then the entanglement problem is discussed for spin-1/2, entangled Markov chains generated by a binary symmetric channel with hopping probability 1-q. The von Neumann entropy of these states, restricted on a sublattice is explicitly calculated and shown to be independent of the size of the sublattice. This is a new, purely quantum, phenomenon. Finally the entanglement property between the sublattices [Formula: see text] and [Formula: see text] is investigated using the PPT criterium. It turns out that, for q≠ 0, 1, ½ the states are non-separable, thus truly entangled, while for q = 0, 1, ½, they are separable.
Gene Expression Profiling of Microsatellite Unstable and Microsatellite Stable Endometrial Cancers Indicates Distinct Pathways of Aberrant Signaling
Authors: Risinger John I. , Maxwell G. Larry , Chandramouli Gadisetti V.R. , Aprelikova Olga , Litzi Tracy , Umar Asad , Berchuck Andrew , Barrett J. Carl 
Published: September 2005

Abstract
Microsatellite instability (MSI) is a molecular phenotype present in ∼25% of endometrial cancers. We examined the global gene expression profiles of early-stage endometrioid endometrial cancers with and without the MSI phenotype to test the hypothesis that MSI phenotype may determine a unique molecular signature among otherwise similar cancers. Unsupervised principal component analysis of the expression data from these cases indicated two distinct groupings of cancers based on MSI phenotype. A relatively small number of array features (392) at high statistical value (P &lt; 0.001) were identified that drive the instability signature in these cancers; 109 of these transcripts differed by at least 2-fold. These data identify distinct gene expression profiles for MSI and microsatellite stable (MSS) cancers, which suggest that cancers with MSI develop in part by different mechanisms from their similar stable counterparts. In particular, we found evidence that two members of the secreted frizzled related protein family (SFRP1 and SFRP4) were more frequently down-regulated in MSI cancers as compared with MSS cancers. Down-regulation was accompanied by promoter hypermethylation for SFRP1. SFRP1 was hypermethylated in 8 of 12 MSI cancers whereas only 3 of 16 MSS cancers were methylated. The WNT target fibroblast growth factor 18 was found to be up-regulated in MSI cancers. These data classify histologically similar endometrioid endometrial cancers into two distinct groupings with implications affecting therapy and prevention.
Escape from Therapy-Induced Accelerated Cellular Senescence in p53-Null Lung Cancer Cells and in Human Lung Cancers
Authors: Roberson Rachel S. , Kussick Steven J. , Vallieres Eric , Chen Szu-Yu J. , Wu Daniel Y. 
Published: September 2005

Abstract
Accelerated cellular senescence (ACS) has been described for tumor cells treated with chemotherapy and radiation. Following exposure to genotoxins, tumor cells undergo terminal growth arrest and adopt morphologic and marker features suggestive of cellular senescence. ACS is elicited by a variety of chemotherapeutic agents in the p53-null, p16-deficient human non–small cell H1299 carcinoma cells. After 10 to 21 days, infrequent ACS cells (1 in 106) can bypass replicative arrest and reenter cell cycle. These cells express senescence markers and resemble the parental cells in their transcription profile. We show that these escaped H1299 cells overexpress the cyclin-dependent kinase Cdc2/Cdk1. The escape from ACS can be disrupted by Cdc2/Cdk1 kinase inhibitors or by knockdown of Cdc2/Cdk1 with small interfering RNA and can be promoted by expression of exogenous Cdc2/Cdk1. We also present evidence that ACS occurs in vivo in human lung cancer following induction chemotherapy. Viable tumors following chemotherapy also overexpress Cdc2/Cdk1. We propose that ACS is a mechanism of in vivo tumor response and that mechanisms aberrantly up-regulate Cdc2/Cdk1 promotes escape from the senescence pathway may be involved in a subset of tumors and likely accounts for tumor recurrence/progression.
A Novel Polypyrimidine Antitumor Agent FdUMP[10] Induces Thymineless Death with Topoisomerase I-DNA Complexes
Authors: Liao Zhi-Yong , Sordet Olivier , Zhang Hong-Liang , Kohlhagen Glenda , Antony Smitha , Gmeiner William H. , Pommier Yves 
Published: September 2005

AbstractFdUMP[10], a 10mer of 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP), the thymidylate synthase inhibitory metabolite of 5-fluorouracil (FU), is most closely correlated with the DNA topoisomerase I (Top1) inhibitor camptothecin in the National Cancer Institute COMPARE analysis, but not with FU. FdUMP[10] exhibits more potent antiproliferative activity than FdUMP or 5-fluoro-2′-deoxyuridine (FdU) and is markedly more active than FU. Camptothecin-resistant P388/CPT45 cells lacking Top1 are cross-resistant to FdUMP[10] as well as to FdUMP, FdU, and the thymidylate synthase inhibitor raltitrexed (Tomudex). FdUMP[10] induces DNA single-strand breaks and cellular Top1-DNA complexes. Such complexes are also observed in response to FdUMP, FdU, raltitrexed, and FU. The FdUMP[10]-induced Top1-DNA complexes are not inhibited by the caspase inhibitor z-VAD-fmk and form independently of apoptotic DNA fragmentation, indicating that they do not correspond to apoptotic Top1-DNA complexes. In biochemical assay, Top1 is directly trapped at uracil and FdU misincorporation sites. We propose that FdUMP[10] damages DNA by trapping Top1 at uracil and FdU misincorporation sites resulting from thymidylate synthase inhibition and thymine depletion.
Leukemic Stem Cells in Childhood High-Risk ALL/t(9;22) and t(4;11) Are Present in Primitive Lymphoid-Restricted CD34+CD19− Cells
Authors: Hotfilder Marc , Röttgers Silja , Rosemann Annegret , Schrauder André , Schrappe Martin , Pieters Rob , Jürgens Heribert , Harbott Jochen , Vormoor Josef 
Published: September 2005

Abstract
Open questions in the pathogenesis of childhood acute lymphoblastic leukemia (ALL) are which hematopoietic cell is target of the malignant transformation and whether primitive stem cells contribute to the leukemic clone. Although good-prognosis ALL is thought to originate in a lymphoid progenitor, it is unclear if this applies to high-risk ALL. Therefore, immature CD34+CD19− bone marrow cells from 8 children with ALL/t(9;22) and 12 with ALL/t(4;11) were purified and analyzed by fluorescence in situ hybridization, reverse transcription-PCR (RT-PCR), and colony assays. Fifty-six percent (n = 8, SD 31%) and 68% (n = 12, SD 26%) of CD34+CD19− cells in ALL/t(9;22) and ALL/t(4;11), respectively, carried the translocation. In addition, 5 of 168 (3%) and 22 of 228 (10%) myeloerythroid colonies expressed BCR/ABL and MLL/AF4. RT-PCR results were confirmed by sequence analysis. Interestingly, in some patients with ALL/t(4;11), alternative splicing was seen in myeloid progenitors compared with the bulk leukemic population, suggesting that these myeloid colonies might be part of the leukemic cell clone. Fluorescence in situ hybridization analysis, however, shows that none of these myeloid colonies (0 of 41 RT-PCR-positive colonies) originated from a progenitor cell that carries the leukemia-specific translocation. Thus, leukemic, translocation-positive CD34+CD19− progenitor/stem cells that were copurified by cell sorting were able to survive in these colony assays for up to 28 days allowing amplification of the respective fusion transcripts by sensitive RT-PCR. In conclusion, we show that childhood high-risk ALL/t(9;22) and t(4;11) originate in a primitive CD34+CD19− progenitor/stem cell without a myeloerythroid developmental potential.
Cancer/Testis Antigen Expression in Human Mesenchymal Stem Cells: Down-regulation of SSX Impairs Cell Migration and Matrix Metalloproteinase 2 Expression
Authors: Cronwright Garth , Le Blanc Katarina , Götherström Cecilia , Darcy Pádraig , Ehnman Monika , Brodin Bertha 
Published: September 2005

Abstract
Several families of genes by and large located on the X chromosome encode proteins of unspecified function. Commonly known as cancer/testis (CT) antigens, they are considered, under normal conditions, only to be expressed in cells of the germ line and placenta. CT genes are also often expressed in cancer cells, hence their classification. Here we report that their expression in normal cells is wider spread and can be observed in cells with the potential for self-renewal and pleuripotency, namely, stem cells. Several CT genes and their products, CT antigens, including SSX, NY-ESO-1, and N-RAGE, were expressed in undifferentiated mesenchymal stem cells (MSCs) and down-regulated after osteocyte and adipocyte differentiation. To elucidate the possible overlapping function played by these genes in cancer and stem cells, a comparative analysis of the localization of their proteins was made. In addition, localization relative to other MSC markers was examined. This revealed that SSX localizes in the cytoplasm and overlap occurs in regions where matrix metalloproteinase 2 (MMP2) and vimentin accumulate. Nevertheless, it was found that no protein interactions between these molecules occur. Further investigation revealed that the migration of a melanoma cell line (DFW), which expresses SSX, MMP2, and vimentin, decreases when SSX is down-regulated. This decrease in cell migration was paralleled by a reduction in MMP2 levels. Analogous to this, SSX expression is down-regulated in MSCs after differentiation; concomitantly a reduction in MMP2 levels occurs. In addition, E-cadherin expression increases, mimicking a mesenchymal epithelial transition. These results afford SSX a functional role in normal stem cell migration and suggest a potentially similar function in cancer cell metastases.
The E7 Protein of Cutaneous Human Papillomavirus Type 8 Causes Invasion of Human Keratinocytes into the Dermis in Organotypic Cultures of Skin
Authors: Akgül Baki , García-Escudero Ramón , Ghali Lucy , Pfister Herbert J. , Fuchs Pawel G. , Navsaria Harshad , Storey Alan 
Published: September 2005

Abstract
Human papillomaviruses (HPV) have been implicated in the development of nonmelanoma skin cancer (NMSC). The molecular mechanisms by which these viruses contribute towards NMSC are poorly understood. We have used an in vitro skin-equivalent model generated by transducing primary adult human epidermal keratinocytes with retroviruses expressing HPV genes to investigate the mechanisms of viral transformation. In this model, keratinocytes expressing HPV genes are seeded onto a mesenchyme composed of deepidermalized human dermis that had been repopulated with primary dermal fibroblasts. Expression of the HPV8 E7 gene caused both an enhancement of terminal differentiation and hyperproliferation, but most strikingly, the acquisition of the ability to migrate and invade through the underlying dermis. The basement membrane integrity was disrupted in a time-dependent manner in areas of invading keratinocytes, as evidenced by immunostaining of its protein components collagen types VII, IV, and laminin 5. This was accompanied by the overexpression of extracellular matrix metalloproteinases MMP-1, MMP-8, and MT-1-MMP. These results suggest that the cutaneous HPV type 8 that is frequently found in NMSC of epidermodysplasia verruciformis patients may actively promote an invasive keratinocyte phenotype. These findings also highlight the importance of epithelial-extracellular matrix-mesenchymal interactions that are required to support cell invasion.
Osteoprotegerin in Prostate Cancer Bone Metastasis
Authors: Corey Eva , Brown Lisha G. , Kiefer Jeffrey A. , Quinn Janna E. , Pitts Tiffany E.M. , Blair Julie M. , Vessella Robert L. 
Published: September 2005

Abstract
Osteoprotegerin (OPG), a critical regulator of osteoclastogenesis, is expressed by prostate cancer cells, and OPG levels are increased in patients with prostate cancer bone metastases. The objective of this study was to investigate the effects of OPG overexpression on prostate cancer cells and prostate cancer/bone cell interactions in vitro and in vivo. OPG-transfected C4-2 cells expressed 8.0 ng OPG per mL per 106 cells, whereas no OPG was detected in the media of C4-2 cells transfected with a control plasmid. OPG overexpressed by C4-2 cells protected these cells from tumor necrosis factor-related apoptosis-inducing ligand–induced apoptosis and decreased osteoclast formation. Subcutaneous OPG-C4-2 and pcDNA-C4-2 tumors exhibited similar growth and take-rate characteristics. However, when grown in bone, tumor volume was decreased in OPG-C4-2 versus pcDNA-C4-2 (P = 0.0017). OPG expressed by C4-2 cells caused increases in bone mineral density (P = 0.0074) and percentage of trabecular bone volume (P = 0.007), and decreases in numbers of osteoblasts and osteoclasts when compared with intratibial pcDNA-C4-2 tumors (P = 0.003 and P = 0.019, respectively). In summary, our data show that increased expression of OPG in C4-2 cells does not directly affect proliferation of prostate cancer cells but indirectly decreases growth of C4-2 tumors in the bone environment. Our data also show that OPG expressed by C4-2 cells inhibits bone lysis associated with C4-2 bone metastasis, which results in net increases in bone volume. We therefore hypothesize that OPG expressed in prostate cancer patient bone metastases may be at least partially responsible for the osteoblastic character of most prostate cancer bone lesions.
Neuropilin-1 Suppresses Tumorigenic Properties in a Human Pancreatic Adenocarcinoma Cell Line Lacking Neuropilin-1 Coreceptors
Authors: Gray Michael J. , Wey Jane S. , Belcheva Anna , McCarty Marya F. , Trevino Jose G. , Evans Douglas B. , Ellis Lee M. , Gallick Gary E. 
Published: September 2005

Abstract
Neuropilin-1 (NRP-1) was first described as a coreceptor implicated in neuronal guidance that bound members of the semaphorin/collapsin family. NRP-1 is also expressed in endothelial cells and is believed to promote angiogenesis by acting as a coreceptor with vascular endothelial growth factor (VEGF) receptor 2. Recent studies suggest that NRP-1 can function through both a VEGF-dependent and VEGF-independent fashion. Expression of NRP-1 has been shown in many human tumors, including pancreatic adenocarcinomas. The exact role of NRP-1 in tumor cells is unknown, particularly in cells that lack the NRP-1 coreceptors VEGF receptor 2 and Plexin-A1. To discern the regulatory role(s) of NRP-1 in pancreatic adenocarcinoma that lack these coreceptors, we overexpressed both full-length NRP-1 and a deletion form of NRP-1 that does not interact with semaphorin or VEGF. Overexpression of either isoform reduced several key tumorigenic properties, including anchorage-independent cell growth and migration in vitro, and resulted in reduced tumor incidence and tumor volume in vivo. Conversely, reduction of NRP-1 expression by small interfering RNA targeting led to enhanced tumor growth. Thus, NRP-1 may play distinct growth regulatory roles in different tumor types, and altering NRP-1 expression or function may be a means of influencing the growth of pancreatic cancers.
Evidence against a Role for SV40 in Human Mesothelioma
Authors: Manfredi James J. , Dong Jianli , Liu Wen-jun , Resnick-Silverman Lois , Qiao Rui , Chahinian Philippe , Saric Marko , Gibbs Allen R. , Phillips James I. , Murray J. , Axten Charles W. , Nolan Robert P. , Aaronson Stuart A. 
Published: September 2005

Abstract
SV40 has been implicated in the etiology of 40% to 60% of human mesotheliomas. These studies could have important medical implications concerning possible sources of human infection and potential therapies if human tumors are induced by this agent. We did PCR-based analysis to detect SV40 large T antigen DNA in human mesotheliomas. None of 69 tumors in which a single copy gene was readily amplified contained detectable SV40 large T antigen sequences. Under these conditions, it was possible to detect one copy of integrated SV40 DNA per cell in a mixture containing a 5,000-fold excess of normal cells using formalin-fixed preparations. Kidney, a known reservoir of SV40 in monkeys, from some of these individuals were also negative for SV40 large T antigen sequences. A subset of mesotheliomas was analyzed for SV40 large T antigen expression by immunostaining with a highly specific SV40 antibody. These tumors as well as several human mesothelioma cell lines previously reported to contain SV40 large T antigen were negative for detection of the virally encoded oncoprotein. Moreover, mesothelioma cell lines with wild-type p53 showed normal p53 function in response to genotoxic stress, findings inconsistent with p53 inactivation by the putative presence of SV40 large T antigen. Taken together, these findings strongly argue against a role of SV40 by any known transformation mechanism in the etiology of the majority of human malignant mesotheliomas.
Breast Cancer Resistance Protein–Mediated Efflux of Androgen in Putative Benign and Malignant Prostate Stem Cells
Authors: Huss Wendy J. , Gray Danny R. , Greenberg Norman M. , Mohler James L. , Smith Gary J. 
Published: September 2005

Abstract
Malignantly transformed stem cells represent a potential common nidus for the primary cancer and the recurrent cancer that arises after treatment failure. Putative prostate stem cells and prostate tumor stem cells in benign and malignant human prostate tissue, in primary human prostate xenografts, and in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model of prostate cancer, are defined by expression of breast cancer resistance protein (BCRP), a marker of pluripotent hematopoietic, muscle, and neural stem cells, and by an absence of androgen receptor (AR) protein. Inhibition of BCRP-mediated efflux of dihydrotestosterone by novobiocin or fumitremorgin C in a rat prostate progenitor cell line that expresses BCRP and AR mRNAs, but minimal AR protein, results in stabilization and nuclear translocation of AR protein, providing a mechanism for lack of AR protein in BCRP-expressing stem cells. In both benign and malignant human prostate tissue, the rare epithelial cells that express BCRP and lack AR protein are localized in the basal cell compartment, survive androgen deprivation, and maintain proliferative potential in the hypoxic, androgen-deprived prostate. Putative prostate tumor stem cells that express BCRP but not AR protein in TRAMP are the source of a BCRP-negative and AR-negative, Foxa2- and SV40Tag-expressing, transit amplifying compartment that progresses to the poorly differentiated carcinomas that arise rapidly after castration. Therefore, BCRP expression isolates prostate stem/tumor stem cells from the prostate tissue microenvironment through constitutive efflux of androgen, protecting the putative tumor stem cells from androgen deprivation, hypoxia, or adjuvant chemotherapy, and providing the nidus for recurrent prostate cancer.