MedWorm: Cytology Top 20

p53 is not directly relevant to the response of Polo-like kinase 1 inhibitors.

Cell Cycle — Tue, 24 Jan 2012 09:52:05 +0100

In this study, we demonstrate that there is no obvious different cytotoxic response between cancer cells with and without functional p53, including the isogenic colon cancer cell lines HCT116p53(+/+) and HCT116p53(-/-), breast cancer cell line MCF7, lung cancer cell line A549 and cervical carcinoma cell line HeLa, after treatment with either siRNA against Plk1, the kinase domain inhibitors BI 2536 and BI 6727 or the PBD inhibitor Poloxin. We suggest that the p53 status is not a predictor for the response of Plk1 inhibition, at least not directly. Yet, the long-term outcomes of losing p53, such as genome instability, could be associated with the cytotoxicity of Plk1 inhibition. Further studies are required to investigate whether other circumstances of cancer cells, such as DNA replication/d...

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Pharmacokinetic analysis of plasma curves obtained after i.v. injection of the PET radioligand [11C] raclopride provides a likely explanation for rapid radioligand metabolism

Journal of Cellular Physiology — Thu, 12 Jan 2012 12:47:31 +0100

AbstractPositron emission tomography (PET) is an imaging technique that provides direct measurements of receptor binding in neurons. The present study was performed to find reasons for the common observation of rapid metabolism of receptor radioligands during time of a brain PET scan. To this aim, the 1‐h phase during which imaging‐data are acquired was evaluated by using a pharmacokinetic approach. The values of half‐lives, volumes of distribution, and dilution calculated for a set of metabolite corrected plasma curves of D2‐receptor radioligand [11C]raclopride (PETc) during 50 min after radioligand injection in tracer dose were compared with the reference values obtained from a set of plasma curves (REFc) during 30 h after i.v. infusion of unlabelled raclopride in pharmacolog...

Mechanisms controlling neurite outgrowth in a pheochromocytoma cell line: The role of TRPC channels

Journal of Cellular Physiology — Thu, 12 Jan 2012 12:46:56 +0100

AbstractTransient Receptor Potential Canonical (TRPC) channels are implicated in modulating neurite outgrowth. The expression pattern of TRPCs changes significantly during brain development, suggesting that fine‐tuning TRPC expression may be important for orchestrating neuritogenesis. To study how alterations in the TRPC expression pattern affect neurite outgrowth, we used nerve growth factor (NGF)‐differentiated rat pheochromocytoma 12 (PC12) cells, a model system for neuritogenesis. In PC12 cells, NGF markedly up‐regulated TRPC1 and TRPC6 expression, but down‐regulated TRPC5 expression while promoting neurite outgrowth. Overexpression of TRPC1 augmented, whereas TRPC5 overexpression decelerated NGF‐induced neurite outgrowth. Conversely, shRNA‐mediated knockdown of TRPC1 decre...

Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations

Aging Cell — Wed, 25 Jan 2012 15:37:46 +0100

SummarySleep:wake cycles break down with age, but the causes of this degeneration are not clear. Using a Drosophila model we addressed the contribution of circadian mechanisms to this aged‐induced deterioration. We found that in old flies free‐running circadian rhythms (behavioral rhythms assayed in constant darkness) have a longer period and an unstable phase before they eventually degenerate. Surprisingly, rhythms are weaker in light:dark cycles and the circadian‐regulated morning peak of activity is diminished under these conditions. On a molecular level, aging results in reduced amplitude of circadian clock gene expression in peripheral tissues. However, oscillations of the clock protein PERIOD (PER) are robust and synchronized among different clock neurons, even in very old, arr...

Inhibition of lung cancer growth: ATP citrate lyase knockdown and statin treatment leads to dual blockade of mitogen‐activated protein Kinase (MAPK) and Phosphatidylinositol‐3‐kinase (PI3K)/AKT pathways

Journal of Cellular Physiology — Thu, 12 Jan 2012 12:47:37 +0100

AbstractATP citrate lyase (ACL) catalyzes the conversion of cytosolic citrate to acetyl‐CoA and oxaloacetate. A definitive role for ACL in tumorigenesis has emerged from ACL RNAi and chemical inhibitor studies, showing that ACL inhibition limits tumor cell proliferation and survival and induces differentiation in vitro. In vivo, it reduces tumor growth leading to a cytostatic effect and induces differentiation. However, the underlying molecular mechanisms are poorly understood and agents that could enhance the efficacy of ACL inhibition have not been identified. Our studies focus on non‐small cell lung cancer (NSCLC) lines, which show phosphatidylinositol 3‐kinase (PI3K)/AKT activation secondary to a mutation in the K‐Ras gene or the EGFR gene. Here we show that ACL knockdown promo...

Mouse model for probing tumor suppressor activity of protein phosphatase 2A in diverse signaling pathways.

Cell Cycle — Tue, 24 Jan 2012 09:52:27 +0100

Authors: Walter G, Ruediger R Abstract Evidence that protein phosphatase 2A (PP2A) is a tumor suppressor in humans came from the discovery of mutations in the genes encoding the Aα and Aβ subunits of the PP2A trimeric holoenzymes, Aα-B-C and Aβ-B-C. One point mutation, Aα-E64D, was found in a human lung carcinoma. It renders Aα specifically defective in binding regulatory B' subunits. Recently, we reported a knock-in mouse expressing Aα-E64D and an Aα knockout mouse. The mutant mice showed a 50-60% increase in the incidence of lung cancer induced by benzopyrene. Importantly, PP2A's tumor suppressor activity depended on p53. These data provide the first direct evidence that PP2A is a tumor suppressor in mice. In addition, they suggest that PP2A is a tumor suppressor in human...

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Bipolar disorder: Kinesin-12 to the rescue.

Cell Cycle — Wed, 11 Jan 2012 16:01:46 +0100

Authors: Dumont J Abstract Comment on: Florian S, et al. Cell Cycle 2011; 10:3533-44. PMID: 22214669 [PubMed - as supplied by publisher] (Source: Cell Cycle)

Interplay between membrane lipid peroxidation, transglutaminase activity, and Cyclooxygenase 2 expression in the tissue adjoining to breast cancer

Journal of Cellular Physiology — Thu, 12 Jan 2012 12:47:18 +0100

AbstractBreast cancer, a leading cause of cancer related deaths worldwide, is one of the most common neoplasms in women. The increased generation of reactive oxygen species (ROS) in breast lesion is critically involved in the mutagenic processes that drive to breast carcinoma initiation and progression. To date, the molecular events occurring in the tissue adjoin the cancer lesion have not been elucidated. Here, we investigated the role of excess ROS generation during human breast carcinogenesis by evaluating oxidative stress biomarkers, tissue transglutaminase (t‐TGase) activity, and expression levels of ubiquitin and cyclooxygenase‐2 (COX‐2) in the normal tissue adjoin to fibroadenoma (nFA), atypical ductal hyperplasia (nADH), and invasive ductal carcinoma (nIDC) from 45 breast can...

A functional cooperativity between Aurora A kinase and LIM kinase1: Implication in the mitotic process.

Cell Cycle — Wed, 11 Jan 2012 16:01:35 +0100

Authors: Ritchey L, Ottman R, Roumanos M, Chakrabarti R Abstract Aurora kinase A (Aur-A), a mitotic kinase, regulates initiation of mitosis through centrosome separation and proper assembly of bipolar spindles. LIM kinase 1 (LIMK1), a modulator of actin and microtubule dynamics, is involved in the mitotic process through inactivating phosphorylation of cofilin. Phosphorylated LIMK1 is recruited to the centrosomes during early prophase, where it colocalizes with γ-tubulin. Here, we report a novel functional cooperativity between Aur-A and LIMK1 through mutual phosphorylation. LIMK1 is recruited to the centrosomes during early prophase and then to the spindle poles, where it colocalizes with Aur-A. Aur-A physically associates with LIMK1 and activates it through phosphorylation, whic...

Disturbances in dental development and craniofacial growth in children treated with hematopoietic stem cell transplantation.

Cell Research — Tue, 24 Jan 2012 13:36:34 +0100

Conclusions - The younger the child is at HSCT, the greater the impairment in dental and vertical facial development. This supports the suggestion that the reduction in lower facial height found in SCT children mainly is a result of impaired dental development and that young age is a risk factor for more severe disturbances. PMID: 22264324 [PubMed - in process] (Source: Cell Research)

Brg1 regulates the transcription of human papillomavirus type 18 E6 and E7 genes.

Cell Cycle — Tue, 24 Jan 2012 09:50:44 +0100

Authors: He H, Luo Y Abstract Integrated high-risk human papillomavirus (HPV) DNA was frequently detected in the genomes of cervical carcinoma cells. The HPV E6 and E7 oncoproteins disrupt the functions of tumor suppressors p53 and Rb; thus, understanding the mechanism by which HPV E6 and E7 gene expression is regulated in cancer cells is highly relevant to cancer biology. Brg1 is a catalytic subunit of the SWI/SNF chromatin remodeling complexes that function in the transcriptional regulation of certain cellular genes. Here, we show that knockdown of Brg1 in HeLa cells leads to cell cycle arrest, p53 and Rb protein accumulation and, interestingly, downregulated expression of HPV18 E6 and E7 genes. Brg1 binds the HPV18 LCR in a JunB- and p300-dependent manner and is required for eff...

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Haploinsufficiency of SGO1 results in deregulated centrosome dynamics, enhanced chromosomal instability and colon tumorigenesis.

Cell Cycle — Tue, 24 Jan 2012 09:52:38 +0100

We report here the generation and characterization of SGO1-mutant mice and show that haploinsufficiency of SGO1 leads to enhanced colonic tumorigenesis. Complete disruption of SGO1 results in embryonic lethality, whereas SGO1 (+/-) mice are viable and fertile. Haploinsufficiency of SGO1 results in genomic instability manifested as missegregation of chromosomes and formation of extra centrosomal foci in both murine embryonic fibroblasts and adult bone marrow cells. Enhanced CIN observed in SGO1-deficient mice resulted in an increase in formation of aberrant crypt foci (ACF) and accelerated development of tumors after exposure to azoxymethane (AOM), a colon carcinogen. Together, these results suggest that haploinsufficiency of SGO1 causes enhanced CIN, colonic preneoplastic lesions and tumor...

Defective trafficking of rhodopsin and its role in retinal degenerations.

International Review of Cell and Molecular Biology — Tue, 24 Jan 2012 11:36:02 +0100

Authors: Hollingsworth TJ, Gross AK Abstract Retinitis pigmentosa is a retinal degeneration transmitted by varied modes of inheritance and affects approximately 1 in 4000 individuals. The photoreceptors of the outer retina, as well as the retinal pigmented epithelium which supports the outer retina metabolically and structurally, are the retinal regions most affected by the disorder. In several forms of retinitis pigmentosa, the mislocalization of the rod photoreceptor protein rhodopsin is thought to be a contributing factor underlying the pathophysiology seen in patients. The mutations causing this mislocalization often occur in genes coding proteins involved in ciliary formation, vesicular transport, rod outer segment disc formation, and stability, as well as the rhodopsin protei...

Differential targeting of androgen and glucocorticoid receptors induces ER stress and apoptosis in prostate cancer cells: A novel therapeutic modality.

Cell Cycle — Wed, 11 Jan 2012 16:00:22 +0100

Authors: Yemelyanov A, Bhalla P, Yang X, Ugolkov A, Iwadate K, Karseladze A, Budunova I Abstract Androgen (AR) and glucocorticoid (GR) receptor signaling play opposing roles in prostate tumorigenesis: in prostate, AR acts as an oncogene, and GR is a tumor suppressor. Recently, we found that non-steroidal phyto-chemical Compound A (CpdA) is AR/GR modulator acting as anti-inflammatory anti-androgen. CpdA inhibits AR and prevents GR transactivation while enhancing GR transrepression. GR and AR are controlled by proteasomal degradation. We found that prolonged exposure of LNCaP, LNCaP-GR, DU145 and PC3 prostate carcinoma (PCa) cells to proteasome inhibitor Bortezomib (BZ) caused AR degradation and GR accumulation. BZ enhanced CpdA ability to inhibit AR and to augment GR transrepression...

Insulin sensitivity after maximal and endurance resistance training.

Cell Research — Tue, 24 Jan 2012 13:38:04 +0100

Authors: Hansen E, Landstad BJ, Gundersen KT, Torjesen PA, Svebak S Abstract Hansen, E, Landstad, BJ, Gundersen, KT, Torjesen, PA, and Svebak, S. Insulin sensitivity after maximal and endurance resistance training. J Strength Cond Res 26(2): 327-334, 2012-The purpose of the study was to compare the effects of maximal resistance training (MRT) vs. endurance resistance training (ERT) on improvements in insulin levels and glucose tolerance in overweight individuals at risk of developing type 2 diabetes. Eighteen participants with baseline values suggesting impaired glucose tolerance were randomly assigned to 1 of 2 groups. Group 1 engaged in supervised MRT (Bernstein inverted pyramid system: 5 × 3-4, 60-85% 1 repetition maximum [1RM]), 3 d·wk over 4 months, whereas members of group ...

The novel expression of Oct3/4 and Bmi1 in the root development of mouse molars

Cell and Tissue Research — Fri, 27 Jan 2012 17:54:29 +0100

This study aimed to investigate the characteristics of the cells involved in the root elongation. Octamer-binding factor 3/4 (Oct3/4) is known as one of the key regulators in maintaining the pluripotency and self-renewal properties of embryonic stem cells. Bmi1, the polycomb-group transcriptional repressor, has emerged as a key regulator in several cellular processes including stem cell self-renewal and cancer cell proliferation. At the beginning of root formation, ameloblasts expressed Oct3/4 in the nucleus, except in the apex of the cervical loop, in which Bmi1and cyclinD were expressed. At PN6, the expression of Oct3/4 in the ameloblasts shifted from the nucleus to the cytoplasm, whereas ameloblastin-negative Hertwig’s epithelial root sheath (HERS) cells expressed Bmi1 and cycli...

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Report of the 2011 annual meeting of the Italian society for virology

Journal of Cellular Physiology — Thu, 19 Jan 2012 05:00:00 +0100

(Source: Journal of Cellular Physiology)

Cell biology of the chloroplast symbiosis in sacoglossan sea slugs.

International Review of Cell and Molecular Biology — Tue, 24 Jan 2012 11:36:02 +0100

Authors: Pierce SK, Curtis NE Abstract Chloroplasts removed from their species of origin may survive for various periods and even photosynthesize in foreign cells. One of the best studied and impressively long, naturally occurring examples of chloroplast persistence, and function inside foreign cells are the algal chloroplasts taken up by specialized cells of certain sacoglossan sea slugs, a phenomenon called chloroplast symbiosis or kleptoplasty. Among sacoglossan species, kleptoplastic associations vary widely in length and function, with some animals immediately digesting chloroplasts, while others maintain functional plastids for over 10 months. Kleptoplasty is a complex process in long-term associations, and research on this topic has focused on a variety of aspects including ...

Periodontal Disease-Associated Compensatory Expression of Osteoprotegerin Is Lost in Type 1 Diabetes Mellitus and Correlates with Alveolar Bone Destruction by Regulating Osteoclastogenesis

Cells Tissues Organs — Tue, 31 Jan 2012 23:00:00 +0100

Cells Tissues Organs (DOI:10.1159/000330879) (Source: Cells Tissues Organs)

Adherens junction assembly and function in the Drosophila embryo.

International Review of Cell and Molecular Biology — Tue, 24 Jan 2012 11:36:02 +0100

Authors: Harris TJ Abstract Adherens junctions are essential for the development and physiology of epithelial tissues. The Drosophila embryo is an excellent model for understanding adherens junction assembly, maintenance, and regulation during tissue development. Here, I review our current state of knowledge in this model system. The review begins by outlining the structure of the cadherin-catenin complex in Drosophila including core (DE-cadherin, Armadillo, α-catenin, and p120-catenin) and peripheral proteins. Then, it summarizes adherens junction assembly at cellularization and maturation at gastrulation. Finally, the regulation of adherens junctions during tissue morphogenesis is discussed. This discussion compares major morphogenetic events in the embryo (invagination of the v...