bluuebunny/crossref_metadata_2025_split huggingface dataset:
SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway
Authors: Shih Yu‐Lueng , Hsieh Chung‐Bao , Lai Hung‐Cheng , Yan Ming‐De , Hsieh Tsai‐Yuan , Chao You‐Chen , Lin Ya‐Wen 
Published: April 2007

AbstractOncogenic activation of the Wnt/β‐catenin signaling pathway is common in hepatocellular carcinoma (HCC). The secreted frizzled‐related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications for carcinogenesis. Promoter hypermethylation of SFRP genes is common in human cancers. However, the role of SFRPs in HCC is not clear. Recently, we have shown that SFRP1 is frequently downregulated through promoter hypermethylation. To confirm and extend these findings, the methylation status of the other SFRP members, including SFRP2, SFRP4 and SFRP5, was examined by methylation‐specific polymerase chain reaction (MS‐PCR). Hypermethylation of SFRP genes, except for SFRP4, is frequent in HCCs and the levels found here were significantly higher than those seen in cirrhotic livers, chronic hepatitis livers and normal controls (p < 0.0001 for SFRP1 and SFRP2, p < 0.05 for SFRP5). To investigate the role of SFRP1 in HCCs, we used re‐expression of SFRP1 in β‐catenin‐dependent HCC cell lines: Huh6 and HepG2. Restoration of SFRP1 attenuated Wnt signaling in those Huh6 hepatoma cells with a β‐catenin gene point mutation, decreased abnormal accumulation of β‐catenin in the nucleus and suppressed cell growth. Conversely, restoration of SFRP1 in HepG2 hepatoma cells with truncated β‐catenin could not block the Wnt signaling pathway. Furthermore, knocking down SFRP1 by RNA interference in β‐catenin‐deficient cell lines (SK‐Hep1) stimulated Wnt signaling and promoted cell growth. Our data suggested that SFRP1 suppressed liver cancer cells growth through Wnt canonical signaling. Moreover, β‐catenin‐independent noncanonical pathway might be involved in Wnt signaling activation through unknown molecules in HCC. © 2007 Wiley‐Liss, Inc.
DOK4/IRS‐5 expression is altered in clear cell renal cell carcinoma
Authors: Al‐sarraf Nael , Reiff Johanne Nørvig , Hinrichsen Jane , Mahmood Shaukat , Teh Bin Tean , McGovern Eilish , De Meyts Pierre , O'Byrne Kenneth J. , Gray Steven G. 
Published: April 2007

AbstractThe insulin‐receptor substrate family plays important roles in cellular growth, signaling, and survival. We have previously shown the dysregulation of the IGF‐axis in clear cell renal cell carcinoma. In this manuscript, we examine the expression of the insulin receptor substrate family in clear cell RCC, and demonstrate that the expression of 2 members of this family are significantly altered in tumors. The most striking finding is that expression of the new IRS family member IRS‐5 is significantly upregulated in 90% of examined clear cell RCCs. Studies on this gene has shown that it is regulated through chromatin remodeling in kidney cells. © 2007 Wiley‐Liss, Inc.
A simple panel unit root test in the presence of cross‐section dependence
Authors: Pesaran M. Hashem 
Published: April 2007

AbstractA number of panel unit root tests that allow for cross‐section dependence have been proposed in the literature that use orthogonalization type procedures to asymptotically eliminate the cross‐dependence of the series before standard panel unit root tests are applied to the transformed series. In this paper we propose a simple alternative where the standard augmented Dickey–Fuller (ADF) regressions are augmented with the cross‐section averages of lagged levels and first‐differences of the individual series. New asymptotic results are obtained both for the individual cross‐sectionally augmented ADF (CADF) statistics and for their simple averages. It is shown that the individual CADF statistics are asymptotically similar and do not depend on the factor loadings. The limit distribution of the average CADF statistic is shown to exist and its critical values are tabulated. Small sample properties of the proposed test are investigated by Monte Carlo experiments. The proposed test is applied to a panel of 17 OECD real exchange rate series as well as to log real earnings of households in the PSID data. Copyright © 2007 John Wiley & Sons, Ltd.
Calcium sulfate–carboxymethylcellulose bone graft binder: Histologic and morphometric evaluation in a critical size defect
Authors: Reynolds Mark A. , Aichelmann‐Reidy Mary E. , Kassolis James D. , Prasad Hari S. , Rohrer Michael D. 
Published: April 2007

AbstractCalcium sulfate (CS) is widely used as a bone graft binder and expander. Recent reports indicate that carboxymethylcellulose (CMC) can improve the clinical properties of CS when used as binder for particulate bone grafts; however, limited information is available on the effects of CMC on bone regeneration. The purpose of this study was to evaluate the histologic and morphometric characteristics of bone formation in calvarial defects grafted with a CS‐based putty containing 10% CMC in combination with allogeneic demineralized bone matrix (DBM). Bone formation and graft/binder resorption were compared with a surgical grade CS and DBM in paired critical‐sized calvarial defects in 25 Wistar rats (350–450 g). Six animals each provided paired defects at 7, 14, 21, and 28 days postsurgery for nondecalcified processing and microscopic analysis. Defects grafted with CS or CS‐CMC putty as the DBM binder exhibited similar patterns and proportions of bone formation, fibrous tissue/marrow, and residual DBM particles. Comparable mean ± SD proportions of new bone formation (31.7 ± 9.5 and 33.7 ± 12.9), fibrous tissue/marrow (54.2 ± 8.3 and 53.0 ± 10.8), residual DBM particles (8.3 ± 6.8 and 10.1 ± 6.3), and residual binder material (5.5 ± 4.6 and 3.7 ± 3.5) were found at 28 days for defects grafted with CS and CS‐CMC putty, respectively. Thus, CMC was found to improve the handling characteristics of CS and, when used in conjunction with DBM, supported comparable levels bone formation and patterns of binder/scaffold resorption as CS and DBM in a calvarial defect model. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Present concepts and future outlook: Function of peroxisome proliferator‐activated receptors (PPARs) for pathogenesis, progression, and therapy of cancer
Authors: Sertznig P. , Seifert M. , Tilgen W. , Reichrath J. 
Published: April 2007

AbstractPeroxisome proliferator‐activated receptors (PPARs) are members of the nuclear receptor superfamily of transcriptional regulators that regulate lipid, glucose, and amino acid metabolism. In recent studies it also has been shown that these receptors are implicated in tumor progression, cellular differentiation, and apoptosis and modulation of their function is therefore considered as a potential target for cancer prevention and treatment. PPAR ligands and other agents influencing PPAR signalling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in a variety of human cancers and could represent a potential novel strategy to inhibit tumor carcinogenesis and progression. This review summarizes the currently available data on the roles of PPARs in relation to the processes of cell differentiation and carcinogenesis as well as their role as promising future therapeutic targets. J. Cell. Physiol. 212: 1–12, 2007. © 2007 Wiley‐Liss, Inc.
Altered intracellular redox status in Gaucher disease fibroblasts and impairment of adaptive response against oxidative stress
Authors: Deganuto Marta , Pittis Maria Gabriela , Pines Alex , Dominissini Silvia , Kelley Mark R. , Garcia Rodolfo , Quadrifoglio Franco , Bembi Bruno , Tell Gianluca 
Published: April 2007

AbstractGaucher disease (GD) is a lysosomal storage disorder, due to glucosylceramide (GlcCer) accumulation in several body tissues, which causes cellular failure by yet unidentified mechanisms. Several evidence indicates that GD pathogenesis is associated to an impairment in intracellular redox state. In fibroblast primary cultures, reactive oxygen species (ROS) levels and protein carbonyl content resulted significantly increased in GD patients compared to healthy donors, suggesting that GD cells, facing a condition of chronic oxidative stress, have evolved an adaptive response to survive. The ROS rise is probably due to NAD(P)H oxidase activity, being inhibited by the treatment with diphenylene iodonium chloride. Interestingly, GD cells are more sensitive to H2O2 induced cell death, suggesting a dysregulation in the adaptive response to oxidative stress in which APE1/Ref‐1 plays a central role. We found that the cytoplasmic amounts of APE1/Ref‐1 protein were significantly higher in GD fibroblasts with respect to controls, and that GD cells failed to upregulate its expression upon H2O2 treatment. Both ROS and APE1/Ref‐1 increases are due to GlcCer accumulation, being prevented by treatment of GD fibroblasts with Cerezyme® and induced in healthy fibroblasts treated with conduritol‐β‐epoxide. These data, suggesting that GD cells display an impairment in the cellular redox state and in the adaptive cellular response to oxidative stress, may open new perspectives in the comprehension of GD pathogenesis. J. Cell. Physiol. 212: 223–235, 2007. © 2007 Wiley‐Liss, Inc.
Retracted: Transcriptional activation by stimulating protein 1 and post‐transcriptional repression by muscle‐specific microRNAs of IKs‐encoding genes and potential implications in regional heterogeneity of their expressions
Authors: Luo Xiaobin , Xiao Jiening , Lin Huixian , Li Baoxin , Lu Yanjie , Yang Baofeng , Wang Zhiguo 
Published: April 2007

AbstractIn cardiac cells, KCNQ1 assembles with KCNE1 and forms a channel complex constituting the slow delayed rectifier current IKs. Expression of KCNQ1 and KCNE1 are regionally heterogeneous and changes with pathological states of the heart. The aims of this study were to decipher the molecular mechanisms for transcriptional and post‐transcriptional regulation expression of KCNQ1 and KCNE1 genes and to shed light on the molecular mechanisms for their spatial heterogeneity of distribution. We cloned the 5′‐flanking region and identified the transcription start sites of the KCNQ1 gene. We characterized the core promoters of KCNQ1 and KCNE1 and revealed the stimulating protein (Sp1) as a common transactivator of KCNQ1 and KCNE1 by interacting with the Sp1 cis‐acting elements in the core promoter regions of these genes. We also characterized the 3′ untranslated regions (3′UTRs) of the genes and experimentally established KCNQ1 and KCNE1 as targets for repression by the muscle‐specific microRNAs miR‐133 and miR‐1, respectively. We demonstrated spatial heterogeneity of KCNQ1 and KCNE1 distributions at three axes (interventricular, transmural and apical‐basal) and disparity between mRNA and protein expressions of these genes. We also found characteristic regional differences of expressions of Sp1 and miR‐1/miR‐133 in the heart. Our study unraveled a novel aspect of the cellular function of miRNAs and suggests that the IKs‐encoding genes KCNQ1 and KCNE1 expressions are dynamically balanced by transcription factor regulation and miRNA repression. The heterogeneities of Sp1 and miR‐1/miR‐133 offer an explanation for the well‐recognized regional differences and disparity between mRNA and protein expressions of KCNQ1 and KCNE1. J. Cell. Physiol. 212: 358–367, 2007. © 2007 Wiley‐Liss, Inc.
M‐CSF‐mediated macrophage differentiation but not proliferation is correlated with increased and prolonged ERK activation
Authors: Suzu Shinya , Hiyoshi Masateru , Yoshidomi Yuka , Harada Hideki , Takeya Motohiro , Kimura Fumihiko , Motoyoshi Kazuo , Okada Seiji 
Published: April 2007

AbstractM‐CSF is a cytokine essential for both the proliferation and differentiation of monocytes/macrophages. In this study, we established a new M‐CSF‐mediated differentiation‐inducing system, and examined how the level and duration of the activation of ERK preceded M‐CSF‐mediated differentiation. TF‐1‐fms human leukemia cells rapidly proliferated in response to M‐CSF. However, in the presence of a phorbol ester, TPA, TF‐1‐fms cells definitely switched their responsiveness to M‐CSF from proliferation to differentiation, as evidenced by a more drastic morphological change and the appearance of cells with a higher level of phagocytic activity. In TF‐1‐fms cells expressing HIV‐1 Nef protein in a conditionally active‐manner, both M‐CSF‐mediated proliferation and M‐CSF/TPA‐mediated differentiation were inhibited by the activation of Nef. The Nef‐active cells showed perturbed patterns of ERK activation. Under the proliferation‐inducing conditions (TPA‐free), parental or Nef‐inactive cells showed modest ERK activation following M‐CSF stimulation, whereas Nef‐active cells showed an earlier and transient ERK activation, despite a decrease in their proliferation rate. Under the differentiation‐inducing conditions, parental or Nef‐inactive cells showed increased and prolonged ERK activation following M‐CSF stimulation, whereas Nef‐active cells showed transient ERK activation. These results supported the idea that the increased and prolonged ERK activation led to M‐CSF‐mediated macrophage differentiation but not to proliferation. J. Cell. Physiol. 212: 519–525, 2007. © 2007 Wiley‐Liss, Inc.
Thapsigargin induces biphasic fragmentation of mitochondria through calcium‐mediated mitochondrial fission and apoptosis
Authors: Hom Jennifer R. , Gewandter Jennifer S. , Michael Limor , Sheu Shey‐Shing , Yoon Yisang 
Published: April 2007

AbstractMitochondrial fission and fusion are the main components mediating the dynamic change of mitochondrial morphology observed in living cells. While many protein factors directly participating in mitochondrial dynamics have been identified, upstream signals that regulate mitochondrial morphology are not well understood. In this study, we tested the role of intracellular Ca2+ in regulating mitochondrial morphology. We found that treating cells with the ER Ca2+‐ATPase inhibitor thapsigargin (TG) induced two phases of mitochondrial fragmentation. The initial fragmentation of mitochondria occurs rapidly within minutes dependent on an increase in intracellular Ca2+ levels, and Ca2+ influx into mitochondria is necessary for inducing mitochondrial fragmentation. The initial mitochondrial fragmentation is a transient event, as tubular mitochondrial morphology was restored as the Ca2+ level decreased. We were able to block the TG‐induced mitochondrial fragmentation by inhibiting mitochondrial fission proteins DLP1/Drp1 or hFis1, suggesting that increased mitochondrial Ca2+ acts upstream to activate the cellular mitochondrial fission machinery. We also found that prolonged incubation with TG induced the second phase of mitochondrial fragmentation, which was non‐reversible and led to cell death as reported previously. These results suggest that Ca2+ is involved in controlling mitochondrial morphology via intra‐mitochondrial Ca2+ signaling as well as the apoptotic process. J. Cell. Physiol. 212: 498–508, 2007. © 2007 Wiley‐Liss, Inc.
Oxidative stress and increased eNOS and NADPH oxidase expression in mouse microvessel endothelial cells
Authors: Ding Hong , Aljofan Mohamad , Triggle Chris R. 
Published: April 2007

AbstractElevated oxidative stress plays a key role in diabetes‐associated vascular disease. In this study, we tested the hypothesis that high glucose‐induced oxidative stress was associated with changes in the expression of NADPH oxidase, superoxide dismutase (SOD) and endothelial nitric oxide synthase (eNOS). Oxidative stress was assessed in cell cultures of mouse microvessel endothelial cells (MMECs) by fluorescence labelling with dihydroethidium, lucigenin‐enhanced chemiluminescence and determining NADPH oxidase subunit and eNOS expression with real‐time polymerase chain reaction protocol and Western blotting. Oxidative stress and expression of the NADPH oxidase subunit, p22phox, were both increased, SOD1 and 3 expression lowered and eNOS significantly elevated in MMECs treated with 40 mM glucose for 72 h compared to low glucose medium. Oxidative stress, p22phox mRNA, eNOS mRNA, and protein were lowered by concurrent incubation with sepiapterin. When eNOS protein expression in endothelial cells was significantly decreased by eNOS siRNA treatment, superoxide generation was significantly higher in the MMECs grown in low glucose, but reduced in those grown in high glucose for 72 h. Thus, exposure of MMECs to high glucose results in increased oxidative stress that is associated with increased eNOS and NADPH oxidase subunit expression, notably p22phox, and decreased expression of SOD1 and 3. J. Cell. Physiol. 212:682–689, 2007. © 2007 Wiley‐Liss, Inc.
14‐3‐3 sigma isoform interacts with the cytoplasmic domain of the transmembrane BP180 in keratinocytes
Authors: Li Yunyuan , Lin Xiaoyue , Kilani Ruhangiz T. , Jones Jonathan C.R. , Ghahary Aziz 
Published: April 2007

AbstractThe protein bullous pemphigoid antigen‐2 (BPAG2/BP180/collagen type XVII) plays a key role in attachment of basal keratinocytes to epidermal basement membrane. The binding of BP180 with either integrin α6, integrin β4, or bullous pemphigoid antigen‐1 (BPAG1/BP230) is critical for this attachment in skin. The protein 14‐3‐3 σ, also known as stratifin and a marker for epithelial cells, is a member of a highly conserved small acidic 14‐3‐3 protein family naturally found in all eukaryotic cells. Here, we have used a 14‐3‐3σ GST pull‐down screening assay and showed that sigma (σ) isoform of the 14‐3‐3 protein family interacts with the cytoplasmic N‐terminal domain of BP180. Analysis of a series of truncated or deleted 14‐3‐3σ revealed that only intact 14‐3‐3σ molecule, but not any of its fragments can interact with BP180. This finding suggests that conformation and possible dimerization of 14‐3‐3 σ is essential for this interaction. Further, a BP180 co‐immunoprecipitation (IP) and its reverse IP assays were conducted and the results confirmed that 14‐3‐3 σ interacts with cytoplasmic domain, but not ecto‐domain of the BP180. In conclusion, the finding of this study provides evidence that 14‐3‐3σ isoform interacts with BP180 which is a major component of hemidesmosome involved in the attachment of epidermis to the basement membrane in skin. However, the significance of this interaction in hemidesmosome formation and/or attachment needs to be explored. J. Cell. Physiol. 212:675–681, 2007. © 2007 Wiley‐Liss, Inc.
Alveolar progenitor cells develop in mouse mammary glands independent of pregnancy and lactation
Authors: Booth Brian W. , Boulanger Corinne A. , Smith Gilbert H. 
Published: April 2007

AbstractWe have previously described pluripotent, parity‐induced mammary epithelial cells (PI‐MEC) marked by Rosa26‐lacZ expression in the mammary glands of parous females. PI‐MEC act as lobule‐limited epithelial stem/progenitor cells. To determine whether parity is necessary to generate PI‐MEC, we incubated mammary explant cultures from virgin mice in vitro with insulin alone (I), hydrocortisone alone (H), prolactin alone (Prl), or a combination of these lactogenic hormones (IHPrl). Insulin alone activated the WAP‐Cre gene. Hydrocortisone and prolactin alone did not. Any combination of hormones that included insulin was effective. Only I, H and Prl together were able to induce secretory differentiation and milk protein synthesis. In addition, EGF, IGF‐2 and IGF‐1 added individually produced activated (lacZ+) PI‐MEC in explant cultures. Neither estrogen nor progesterone induced WAP‐Cre expression in the explants. None of these positive initiators of WAP‐Cre expression in PI‐MEC were effective in mammospheres or two‐dimensional cultures of mammary epithelium, indicating the indispensability of epithelial–stromal interaction in PI‐MEC activation. Like PI‐MEC, lacZ+ cells from virgin explants proliferated and contributed progeny to mammospheres in vitro and to epithelial outgrowths in vivo after transplantation. LacZ+ cells induced in virgin mouse mammary explants were multipotent (like PI‐MEC) in impregnated hosts producing lacZ+ mammary alveolar structures comprised of both myoepithelial and luminal progeny. These data demonstrate PI‐MEC, a mammary epithelial sub‐population of lobule‐limited progenitor cells, are present in nulliparous female mice before parity and, like the PI‐MEC observed following parity, are capable of proliferation, self‐renewal and the capacity to produce progeny of diverse epithelial cell fates. J. Cell. Physiol. 212:729–736, 2007. © 2007 Wiley‐Liss, Inc.
Dual regulation of upstream binding factor 1 levels by IRS‐1 and ERKs in IGF‐1‐receptor signaling
Authors: Sun Hongzhi , Tu Xiao , Liu Mingli , Baserga Renato 
Published: April 2007

AbstractThe Upstream Binding Factor 1 (UBF1) is a nucleolar protein that participates in the regulation of RNA polymerase I activity and ribosomal RNA (rRNA) synthesis. In 32D myeloid cells expressing the type 1 insulin‐like growth factor receptor (IGF‐IR), the UBF1 protein (but not its mRNA) is down regulated when the cells are shifted from Interleukin‐3 (IL‐3) to IGF‐1. Ectopic expression of insulin receptor substrate‐1 (IRS‐1) in these cells inhibits the down‐regulation of UBF1. We now show that the stability of UBF1 in 32D‐derived cells requires also a signal from the extracellular regulated kinases (ERKs). When ERKs signaling is defective, as in cells over‐expressing the insulin receptor (InR) or selected mutants of the IGF‐1R, UBF1 is down‐regulated, even in the presence of IRS‐1. The down‐regulation is corrected by the expression of an activated Ha‐ras, which stimulates ERKs activity. Mutations at threonines 117 and 201 of UBF1, known to be phosphorylated by ERKs, cause its down‐regulation. However, when IRS‐2, instead of IRS‐1, is ectopically expressed in 32D InR cells, ERKs phosphorylation is increased and UBF is stabilized. Taken together, these results indicate that in 32D‐derived myeloid cells expressing either the IGF‐IR or the InR, UBF1 levels are regulated by signaling from both IRS proteins and ERKs. J. Cell. Physiol. 212:780–786, 2007. © 2007 Wiley‐Liss, Inc.
Zinc regulates the ability of Cdc25C to activate MPF/cdk1
Authors: Sun Lu , Chai Yingtao , Hannigan Robyn , Bhogaraju Venkata K. , Machaca Khaled 
Published: April 2007

AbstractZn2+ is an essential micronutrient for the growth and development of multicellular organisms, as Zn2+ deficiencies lead to growth retardation and congenital malformations (Vallee, BL, Falchuk, KH. 1993. Physiol Rev., 73:79–118). At the cellular level Zn2+ depravation results in proliferation defects in many cell types (Vallee, BL, Falchuk, KH. 1993. Physiol Rev., 73:79–118), however the molecular pathways involved remain poorly defined. Here we show that the transition metal chelator TPEN (N,N,N′,N′‐tetrakis(2‐pyridylmethyl) ethylene diamine) blocks the G2/M transition of the meiotic cell cycle by inhibiting Cdc25C‐cdk1 activation. ICP‐MS analyses reveal that Cdc25C is a Zn2+‐binding metalloprotein, and that TPEN effectively strips Zn2+ away from the enzyme. Interestingly, although apo‐Cdc25C (Zn2+‐deficient) remains fully catalytically active, it is compromised in its ability to dephosphorylate and activate MPF/cdk1. Thus, Zn2+ is an important regulator of Cdc25C function in vivo. Because of the conserved essential role of the Cdc25C‐cdk1 module in the eukaryotic cell cycle, these studies provide fundamental insights into cell cycle regulation. J. Cell. Physiol. 213: 98–104, 2007. © 2007 Wiley‐Liss, Inc.