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Pre-Mrna Secondary Structures Influence Exon Recognition, Michael Hiller, Zhaiyi Zhang, Rolf Backofen, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

The secondary structure of a pre-mRNA influences a number of processing steps including alternative splicing. Since most splicing regulatory proteins bind to single-stranded RNA, the sequestration of RNA into double strands could prevent their binding. Here, we analyzed the secondary structure context of experimentally determined splicing enhancer and silencer motifs in their natural pre-mRNA context. We found that these splicing motifs are significantly more single-stranded than controls. These findings were validated by transfection experiments, where the effect of enhancer or silencer motifs on exon skipping was much more pronounced in single-stranded conformation. We also found that the structural context of …

Discovery Of Platelet-Type 12-Human Lipoxygenase Selective Inhibitors By High-Throughput Screening Of Structurally Diverse Libraries., Joshua D. Deschamps, Jeffrey T. Gautschi, Stephanie Whitman, Tyler A. Johnson, Nadine C. Gassner, Phillip Crews, Theodore R. Holman

Natural Sciences and Mathematics | Faculty Scholarship

Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharmaceutical therapeutics. To this end, we have modified a known lipoxygenase assay for high-throughput (HTP) screening of both the National Cancer Institute (NCI) and the UC Santa Cruz marine extract library (UCSC-MEL) in search of platelet-type 12-hLO (12-hLO) selective inhibitors. The HTP screen led to the characterization of five novel 12-hLO inhibitors …

Adaptive Radiotherapy Planning On Decreasing Gross Tumor Volumes As Seen On Megavoltage Computed Tomography Images., Curtis Woodford, Slav Yartsev, R. Dar, Glenn Bauman, Jacob Van Dyk

Oncology Publications

PURPOSE: To evaluate gross tumor volume (GTV) changes for patients with non-small-cell lung cancer by using daily megavoltage (MV) computed tomography (CT) studies acquired before each treatment fraction on helical tomotherapy and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV.

METHODS AND MATERIALS: Seventeen patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for non-small-cell lung cancer at London Regional Cancer Program from Dec 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kilovoltage CT image sets to investigate the advantages …

Micro Rna 145 Targets The Insulin Receptor Substrate-1 And Inhibits The Growth Of Colon Cancer Cells, Bin Shi, Laura Sepp-Lorenzino, Marco Prisco, Peter Linsley, Tiziana Deangelis, Renato Baserga

Department of Cancer Biology Faculty Papers

The insulin receptor substrate-1 (IRS-1), a docking protein for both the type 1 insulin-like growth factor receptor (IGF-IR) and the insulin receptor, is known to send a mitogenic, anti-apoptotic, and anti-differentiation signal. Several micro RNAs (miRs) are suggested by the data base as possible candidates for targeting IRS-1. We show here that one of the miRs predicted by the data base, miR145, whether transfected as a synthetic oligonucleotide or expressed from a plasmid, causes down-regulation of IRS-1 in human colon cancer cells. IRS-1 mRNA is not decreased by miR145, while it is down-regulated by an siRNA targeting IRS-1. Targeting of …

Clinic Variation In The Cost-Effectiveness Of Contingency Management, Todd A. Olmstead, Nancy M. Petry

UCHC Articles - Research

This study determined whether, and by how much, the cost-effectiveness of contingency management (CM) varied across the eight clinics in the National Institute on Drug Abuse Clinical Trials Network MIEDAR trial. Incremental costs, incremental outcomes, and incremental costeffectiveness ratios (ICERs) of CM compared to usual care were calculated, compared and contrasted for each of the clinics. Results showed that the incremental cost of using CM compared to usual care varied by a factor of 1.9 across the clinics, ranging from an additional $306 to an additional $582 per patient. The effect of CM on the longest duration of continuous stimulant …

Developing "Human Functioning And Rehabilitation Research" From The Comprehensive Perspective., Gerold Stucki, Jan Dietrich Reinhardt, Gunnar Grimby, John Melvin

Department of Rehabilitation Medicine Faculty Papers

With the International Classification of Functioning, Disability and Health (ICF) the World Health Organization (WHO) has prepared the ground for a comprehensive understanding of Human Functioning and Rehabilitation Research, integrating the biomedical perspective on impairment with the social model of disability. This poses a number of old and new challenges regarding the enhancement of adequate research capacity. Here we will summarize approaches to address these challenges with respect to 3 areas: the organization of Human Functioning and Rehabilitation Research into distinct scientific fields, the development of suitable academic training programmes and the building of university centres and collaboration networks.

Human Tob, An Antiproliferative Transcription Factor, Is A Poly(A)-Binding Protein-Dependent Positive Regulator Of Cytoplasmic Mrna Deadenylation, Nader Ezzeddine, Tsung-Cheng Chang, Wenmiao Zhu, Akio Yamashita, Chyi-Ying A Chen, Zhenping Zhong, Yukiko Yamashita, Dinghai Zheng, Ann-Bin Shyu

Faculty, Staff and Student Publications

In mammalian cells, mRNA decay begins with deadenylation, which involves two consecutive phases mediated by the PAN2-PAN3 and the CCR4-CAF1 complexes, respectively. The regulation of the critical deadenylation step and its relationship with RNA-processing bodies (P-bodies), which are thought to be a site where poly(A)-shortened mRNAs get degraded, are poorly understood. Using the Tet-Off transcriptional pulsing approach to investigate mRNA decay in mouse NIH 3T3 fibroblasts, we found that TOB, an antiproliferative transcription factor, enhances mRNA deadenylation in vivo. Results from glutathione S-transferase pull-down and coimmunoprecipitation experiments indicate that TOB can simultaneously interact with the poly(A) nuclease complex CCR4-CAF1 and …

Is A 3-Mm Intrafractional Margin Sufficient For Daily Image-Guided Intensity-Modulated Radiation Therapy Of Prostate Cancer?, Adam D Melancon, Jennifer C O'Daniel, Lifei Zhang, Rajat J Kudchadker, Deborah A Kuban, Andrew K Lee, Rex M Cheung, Renaud De Crevoisier, Susan L Tucker, Wayne D Newhauser, Radhe Mohan, Lei Dong

Faculty, Staff and Student Publications

PURPOSE: To determine whether a 3-mm isotropic target margin adequately covers the prostate and seminal vesicles (SVs) during administration of an intensity-modulated radiation therapy (IMRT) treatment fraction, assuming that daily image-guided setup is performed just before each fraction.

MATERIALS AND METHODS: In-room computed tomographic (CT) scans were acquired immediately before and after a daily treatment fraction in 46 patients with prostate cancer. An eight-field IMRT plan was designed using the pre-fraction CT with a 3-mm margin and subsequently recalculated on the post-fraction CT. For convenience of comparison, dose plans were scaled to full course of treatment (75.6 Gy). Dose coverage …

Sirtuins, Nuclear Hormone Receptor Acetylation And Transcriptional Regulation, James R. Whittle, Michael J. Powell, Vladimir M. Popov, L. Andrew Shirley, Chenguang Wang, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Endocrine signaling via nuclear receptors (NRs) is known to play an important role in normal physiology as well as in human tumor progression. Hormones regulate gene expression by altering local chromatin structure and, thereby, accessibility of transcriptional co-regulators to DNA. Recently it has been shown that non-histone proteins involved in hormone signaling, such as nuclear receptors and NR co-activators, are regulated by acetylation, resulting in their altered transcriptional activity. NAD-dependent protein deacetylases, the sirtuins (Sir2-related enzymes), directly modify NRs. Because sirtuins have been shown to regulate tumor cellular growth, aging, metabolic signaling and endocrine hormone signaling, they might play a …

Dissociating Speech Perception And Comprehension At Reduced Levels Of Awareness, Matthew H Davis, Martin R Coleman, Anthony R Absalom, Jennifer M Rodd, Ingrid Johnsrude, Basil F Matta, Adrian M Owen, David K Menon

Brain and Mind Institute Researchers' Publications

We used functional MRI and the anesthetic agent propofol to assess the relationship among neural responses to speech, successful comprehension, and conscious awareness. Volunteers were scanned while listening to sentences containing ambiguous words, matched sentences without ambiguous words, and signal-correlated noise (SCN). During three scanning sessions, participants were nonsedated (awake), lightly sedated (a slowed response to conversation), and deeply sedated (no conversational response, rousable by loud command). Bilateral temporal-lobe responses for sentences compared with signal-correlated noise were observed at all three levels of sedation, although prefrontal and premotor responses to speech were absent at the deepest level of sedation. Additional …

Nicotinamide Riboside Kinase Structures Reveal New Pathways To Nad+, Wolfram Tempel, Wael M. Rabeh, Katrina L. Bogan, Peter Belenky, Marzena Wojcik, Heather F. Seidle, Lyudmila Nedyalkova, Tianle Yang, Anthony A. Sauve, Hee-Won Park, Charles Brenner

Dartmouth Scholarship

The eukaryotic nicotinamide riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize …

Human Parietal "Reach Region" Primarily Encodes Intrinsic Visual Direction, Not Extrinsic Movement Direction, In A Visual Motor Dissociation Task., Juan Fernandez-Ruiz, Herbert C Goltz, Joseph F X Desouza, Tutis Vilis, J Douglas Crawford

Brain and Mind Institute Researchers' Publications

Posterior parietal cortex (PPC) participates in the planning of visuospatial behaviors, including reach movements, in gaze-centered coordinates. It is not known if these representations encode the visual goal in retinal coordinates, or the movement direction relative to gaze. Here, by dissociating the intrinsic retinal stimulus from the extrinsic direction of movement, we show that PPC employs a visual code. Using delayed pointing and event-related functional magnetic resonance imaging, we identified a cluster of PPC regions whose activity was topographically (contralaterally) related to the direction of the planned movement. We then switched the normal visual-motor spatial relationship by adapting subjects to …

Do Vegetative Patients Retain Aspects Of Language Comprehension? Evidence From Fmri, Martin R Coleman, Jennifer M Rodd, Matthew H Davis, Ingrid Johnsrude, David K Menon, John D Pickard, Adrian M Owen

Brain and Mind Institute Researchers' Publications

A diagnosis of vegetative state is made if a patient demonstrates no evidence of awareness of self or environment, no evidence of sustained, reproducible, purposeful or voluntary behavioural response to sensory stimuli and critically no evidence of language comprehension. For those patients who retain peripheral motor function, rigorous behavioural assessment is usually able to determine retained function. However, some patients do not retain the ability to respond overtly to command and it is becoming increasingly accepted that assessment of these patients should include techniques, which do not rely on any 'motor action' on the part of the patient. Here, we …

Effects Of Atomoxetine On Growth In Children With Attention-Deficit/Hyperactivity Disorder Following Up To Five Years Of Treatment., Thomas J. Spencer, Christopher J. Kratochvil, R. Bart Sangal, Keith E. Saylor, Charles E. Bailey, David W. Dunn, Daniel A. Geller, Charles D. Casat, Robert S. Lipetz, Rakesh Jain, Jeffrey H. Newcorn, Dustin D. Ruff, Peter D. Feldman, Amanda J. Furr, Albert J. Allen

Journal Articles: Psychiatry

OBJECTIVE: To examine the effects on growth of long-term pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), we present findings from an ongoing 5-year study of the efficacy and safety of treatment with atomoxetine.

METHODS: North American patients, 6-17 years old at study entry (N = 1,312) and with Diagnostic and Statistical Manual of Mental Disorders,4th edition (DSM-IV) ADHD, were studied under open-label atomoxetine treatment. Sixty-one were studied up to 5 years.

RESULTS: After 1 month's treatment, patients weighed less than expected from their starting percentiles relative to population norms, with a maximum shortfall at 15 months and a return to expected …

Rhabdomyolysis After Laparoscopic Nephrectomy., Deborah T. Glassman, William G. Merriam, Edouard J. Trabulsi, Dolores Byrne, Leonard Gomella

Department of Urology Faculty Papers

BACKGROUND AND OBJECTIVES: Laparoscopic renal surgery has become a widely applied technique in recent years. The development of postoperative rhabdomyolysis is a known but rare complication of laparoscopic renal surgery. Herein, 4 cases of rhabdomyolysis and a review of the literature are presented with respect to pathogenesis, treatment, and prevention of this dire complication. METHODS: A retrospective review of over 600 laparoscopic renal operations over the past 8 years was performed. All cases of postoperative rhabdomyolysis were identified. A Medline search was performed to find articles related to the development of postoperative rhabdomyolysis. Cases of rhabdomyolysis developing after laparoscopic renal …

Mutations In The Cofilin Partner Aip1/Wdr1 Cause Autoinflammatory Disease And Macrothrombocytopenia, Benjamin T Kile, Athanasia D Panopoulos, Roslynn A Stirzaker, Douglas F Hacking, Lubna H Tahtamouni, Tracy A Willson, Lisa A Mielke, Katya J Henley, Jian-Guo Zhang, Ian P Wicks, William S Stevenson, Paquita Nurden, Stephanie S Watowich, Monica J Justice

Faculty, Staff and Student Publications

A pivotal mediator of actin dynamics is the protein cofilin, which promotes filament severing and depolymerization, facilitating the breakdown of existing filaments, and the enhancement of filament growth from newly created barbed ends. It does so in concert with actin interacting protein 1 (Aip1), which serves to accelerate cofilin's activity. While progress has been made in understanding its biochemical functions, the physiologic processes the cofilin/Aip1 complex regulates, particularly in higher organisms, are yet to be determined. We have generated an allelic series for WD40 repeat protein 1 (Wdr1), the mammalian homolog of Aip1, and report that reductions in Wdr1 function …

Downregulation Of Rap1gap Contributes To Ras Transformation, Oxana Tsygankova, Gregory V. Prendergast, Kanchan Puttaswamy, Yan Wang, Michael D. Feldman, Hongbin Wang, Marcia S. Brose, Judy L. Meinkoth

Faculty, Staff and Student Publications

Although abundant in well-differentiated rat thyroid cells, Rap1GAP expression was extinguished in a subset of human thyroid tumor-derived cell lines. Intriguingly, Rap1GAP was downregulated selectively in tumor cell lines that had acquired a mesenchymal morphology. Restoring Rap1GAP expression to these cells inhibited cell migration and invasion, effects that were correlated with the inhibition of Rap1 and Rac1 activity. The reexpression of Rap1GAP also inhibited DNA synthesis and anchorage-independent proliferation. Conversely, eliminating Rap1GAP expression in rat thyroid cells induced a transient increase in cell number. Strikingly, Rap1GAP expression was abolished by Ras transformation. The downregulation of Rap1GAP by Ras required the …

Versatile Applications Of Transcriptional Pulsing To Study Mrna Turnover In Mammalian Cells, Chyi-Ying A Chen, Yukiko Yamashita, Tsung-Cheng Chang, Akio Yamashita, Wenmiao Zhu, Zhenping Zhong, Ann-Bin Shyu

Faculty, Staff and Student Publications

Development of transcriptional pulsing approaches using the c-fos and Tet-off promoter systems greatly facilitated studies of mRNA turnover in mammalian cells. However, optimal protocols for these approaches vary for different cell types and/or physiological conditions, limiting their widespread application. In this study, we have further optimized transcriptional pulsing systems for different cell lines and developed new protocols to facilitate investigation of various aspects of mRNA turnover. We apply the Tet-off transcriptional pulsing strategy to investigate ARE-mediated mRNA decay in human erythroleukemic K562 cells arrested at various phases of the cell cycle by pharmacological inhibitors. This application facilitates studies of the …

Computational Identification And Functional Validation Of Regulatory Motifs In Cartilage-Expressed Genes, Sherri R Davies, Li-Wei Chang, Debabrata Patra, Xiaoyun Xing, Karen Posey, Jacqueline Hecht, Gary D Stormo, Linda J Sandell

Faculty, Staff and Student Publications

Chondrocyte gene regulation is important for the generation and maintenance of cartilage tissues. Several regulatory factors have been identified that play a role in chondrogenesis, including the positive transacting factors of the SOX family such as SOX9, SOX5, and SOX6, as well as negative transacting factors such as C/EBP and delta EF1. However, a complete understanding of the intricate regulatory network that governs the tissue-specific expression of cartilage genes is not yet available. We have taken a computational approach to identify cis-regulatory, transcription factor (TF) binding motifs in a set of cartilage characteristic genes to better define the transcriptional regulatory …

Regulation Of Mucin Gene Expression By Creb Via A Nonclassical Retinoic Acid Signaling Pathway, Seung-Wook Kim, Jeong Soo Hong, Seung-Hee Ryu, Wen-Cheng Chung, Joo-Heon Yoon, Ja Seok Koo

Faculty, Staff and Student Publications

Vitamin A and its metabolite retinoic acid (RA) are essential elements for normal lung development and the differentiation of lung epithelial cells. We previously showed that RA rapidly activated cyclic AMP response element-binding protein (CREB) in a nonclassical manner in normal human tracheobronchial epithelial (NHTBE) cells. In the present study, we further demonstrated that this nonclassical signaling of RA on the activation of CREB plays a critical role in regulating the expression of airway epithelial cell differentiation markers, the MUC2, MUC5AC, and MUC5B genes. We found that RA rapidly activates the protein kinase Calpha isozyme and transmits the activation signal …

Selective Repression Of Retinoic Acid Target Genes By Rip140 During Induced Tumor Cell Differentiation Of Pluripotent Human Embryonal Carcinoma Cells, Kelly C. Heim, Kristina A. White, Dexin Deng, Craig R. Tomlinson, Jason Moore, Sarah Freemantle, Michael Spinella

Dartmouth Scholarship

The use of retinoids as anti-cancer agents has been limited due to resistance and low efficacy. The dynamics of nuclear receptor coregulation are incompletely understood. Cell-and context-specific activities of nuclear receptors may be in part due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We had previously shown that RIP140 limits RA induced tumor cell differentiation of embryonal carcinoma; the pluriopotent stem cells of testicular germ cell tumors. This implies that RIP140 represses key genes required for RA-mediated tumor cell differentiation. Identification …

Microvascular Endothelial Cells Express A Phosphatidylserine Receptor: A Functionally Active Receptor For Phosphatidylserine-Positive Erythrocytes, Yamaja Setty, Suhita Gayen Betal

Department of Pediatrics Faculty Papers

Phosphatidylserine (PS)-positive erythrocytes adhere to endothelium and subendothelial matrix components. While thrombospondin mediates these inter-actions, it is unknown whether PS-associated erythrocyte-endothelial adhesion occurs in the absence of plasma ligands. Using ionophore-treated PS-expressing control HbAA erythrocytes, we demonstrate that PS-positive erythrocytes adhered to human lung microendothelial cells in the absence of plasma ligands, that this adhesion was enhanced following endothelial activation with IL-1alpha, TNF-alpha, LPS, hypoxia, and heme, and that this adhesive interaction was selective to erythrocyte PS. We next explored whether microendothelial cells express an adhesion receptor that recognizes cell surface-expressed PS (PSR) similar to that expressed on activated macrophages. …

Patient Involvement In Patient Safety: What Factors Influence Patient Participation And Engagement?, Rachel Davis, Rosamond Jacklin, Nick Sevdalis, Charles A. Vincent

Faculty Publications

BACKGROUND: Patients can play an important role in improving patient safety by becoming actively involved in their health care. However, there is a paucity of empirical data on the extent to which patients take on such a role. In order to encourage patient participation in patient safety we first need to assess the full range of factors that may be implicated in such involvement. OBJECTIVE: To delineate factors that could affect the participation of the patient in quality and safety issues in their health care. METHOD: Literature review of patient involvement in health care, drawing from direct evidence (specifically from …

Receiver Operating Characteristic And Location Analysis Of Simulated Near-Infrared Tomography Images, Xiaomei Song, Brian W. Pogue, Hamid Dehghani, Shudong Jiang, Keith D. Paulsen, Tor D. Tosteson

Dartmouth Scholarship

Receiver operating characteristic (ROC) analysis was performed on simulated near-infrared tomography images, using both human observer and contrast-to-noise ratio (CNR) computational assessment, for application in breast cancer imaging. In the analysis, a nonparametric approach was applied for estimating the ROC curves. Human observer detection of objects had superior capability to localize the presence of heterogeneities when the objects were small with high contrast, with a minimum detectable threshold of CNR near 3.0 to 3.3 in the images. Human observers were able to detect heterogeneities in the images below a size limit of 4 mm, yet could not accurately find the …

Funding Crisis In Title Vii Diversity Programs, Paula N O'Neill, Alvin H Strelnick

Faculty, Staff and Student Publications

No abstract provided.

Recent Advances In Cancer Stem/Progenitor Cell Research: Therapeutic Implications For Overcoming Resistance To The Most Aggressive Cancers., M. Mimeault, Ralph Hauke, Parmender P. Mehta, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Overcoming intrinsic and acquired resistance of cancer stem/progenitor cells to current clinical treatments represents a major challenge in treating and curing the most aggressive and metastatic cancers. This review summarizes recent advances in our understanding of the cellular origin and molecular mechanisms at the basis of cancer initiation and progression as well as the heterogeneity of cancers arising from the malignant transformation of adult stem/progenitor cells. We describe the critical functions provided by several growth factor cascades, including epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), stem cell factor (SCF) receptor (KIT), hedgehog and Wnt/beta-catenin signalling pathways that …

Evaluating The Effectiveness Of Psychosocial Interventions For Individuals With Visible Differences: A Systematic Review Of The Empirical Literature., Alyson Bessell, Timothy P. Moss

More Faculty of Health Research

The objective of this review was to systematically identify and evaluate all known studies testing empirically the efficacy of psychosocial intervention programmes for adults with visible differences. Twelve papers met the inclusion criteria. None of the papers demonstrated adequately the clinical effectiveness of the interventions. The review concluded that further research was needed to demonstrate adequately the effectiveness of existing interventions, and a greater number of Randomised Controlled Trials and experimental studies were required to increase the methodological validity of intervention studies.

The Shift From Defined Benefit Pensions To 401(K) Plans And The Pension Assets Of The Baby Boom Cohort, James Poterba, Steven Venti, David A. Wise

Dartmouth Scholarship

The rise of 401(k) plans and the decline of defined benefit plans will have an important effect on the wealth of future retirees. Changing demographic structure also will affect the aggregate stock of retirement wealth. We project the stock of assets held in retirement plans and the average retirement saving of retirees through 2040. Our projections show large increases in wealth at retirement, especially if the returns on corporate equities are comparable with historical returns. Retirement wealth will grow, however, even if equity returns fall substantially below their historical level.

Human Collagen Krox Up-Regulates Type I Collagen Expression In Normal And Scleroderma Fibroblasts Through Interaction With Sp1 And Sp3 Transcription Factors., Magdalini Kypriotou, Gallic Beauchef, Christos Chadjichristos, Russell Widom, Emmanuelle Renard, Sergio A. Jimenez, Joseph Korn, François-Xavier Maquart, Thierry Oddos, Otto Von Stetten, Jean-Pierre Pujol, Philippe Galéra

Department of Medicine Faculty Papers

Despite several investigations, the transcriptional mechanisms that regulate the expression of both type I collagen genes (COL1A1 and COL1A2) in either physiological or pathological situations, such as scleroderma, are not completely known. We have investigated the role of hc-Krox transcription factor on type I collagen expression by human dermal fibroblasts. hc-Krox exerted a stimulating effect on type I collagen protein synthesis and enhanced the corresponding mRNA steady-state levels of COL1A1 and COL1A2 in foreskin fibroblasts (FF), adult normal fibroblasts (ANF), and scleroderma fibroblasts (SF). Forced hc-Krox expression was found to up-regulate COL1A1 transcription through a -112/-61-bp sequence in FF, ANF, …

Human Muc4 Mucin Induces Ultra-Structural Changes And Tumorigenicity In Pancreatic Cancer Cells., N. Moniaux, P. Chaturvedi, G. C. Varshney, Jane L. Meza, J. F. Rodriguez-Sierra, J-P Aubert, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is a type-1 transmembrane glycoprotein and is overexpressed in many carcinomas. It is a heterodimeric protein of 930 kDa, composed of a mucin-type subunit, MUC4alpha, and a membrane-bound growth factor-like subunit, MUC4beta. MUC4 mRNA contains unique 5' and 3' coding sequences along with a large variable number of tandem repeat (VNTR) domain of 7-19 kb. A direct association of MUC4 overexpression has been established with the degree of invasiveness and poor prognosis of pancreatic cancer. To understand the precise role of MUC4 in pancreatic cancer, we engineered a MUC4 complementary DNA construct, mini-MUC4, whose deduced protein (320 kDa) is …