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Articles 1 - 9 of 9
Full-Text Articles in Medical Molecular Biology
Id4 Deficiency Attenuates Prostate Development And Promotes Pin-Like Lesions By Regulating Androgen Receptor Activity And Expression Of Nkx3.1 And Pten, Pankaj Sharma, Ashley Knowell, Swathi Chinaranagari, Shravan Komaragiri, Peri Nagappan, Divya Patel, Mathew C. Havrda, Jaideep Chaudhary
Id4 Deficiency Attenuates Prostate Development And Promotes Pin-Like Lesions By Regulating Androgen Receptor Activity And Expression Of Nkx3.1 And Pten, Pankaj Sharma, Ashley Knowell, Swathi Chinaranagari, Shravan Komaragiri, Peri Nagappan, Divya Patel, Mathew C. Havrda, Jaideep Chaudhary
Dartmouth Scholarship
Background: Inhibitor of differentiation 4 (Id4), a member of the helix-loop-helix family of transcriptional regulators has emerged as a tumor suppressor in prostate cancer. Id4 is expressed in the normal prostate where its expression is also regulated by androgens. In this study we investigated the effect of loss of Id4 (Id4-/-) on adult prostate morphology. Methods: Histological analysis was performed on prostates from 6-8 weeks old Id4-/-, Id4+/- and Id4+/+ mice. Expression of Id1, Sox9, Myc, androgen receptor, Akt, p-Akt, Pten and Nkx3.1 was investigated by immunohistochemistry. Androgen receptor binding on NKX3.1 promoter was studied by chromatin immuno-precipitation. Id4 was …
Pilot Study Of Cyp2b6 Genetic Variation To Explore The Contribution Of Nitrosamine Activation To Lung Carcinogenesis, Catherine Wassenaar, Qiong Dong, Christopher Amos, Margaret Spitz, Rachel F. Tyndale
Pilot Study Of Cyp2b6 Genetic Variation To Explore The Contribution Of Nitrosamine Activation To Lung Carcinogenesis, Catherine Wassenaar, Qiong Dong, Christopher Amos, Margaret Spitz, Rachel F. Tyndale
Dartmouth Scholarship
We explored the contribution of nitrosamine metabolism to lung cancer in a pilot investigation of genetic variation in CYP2B6, a high-affinity enzymatic activator of tobacco-specific nitrosamines with a negligible role in nicotine metabolism. Previously we found that variation in CYP2A6 and CHRNA5-CHRNA3-CHRNB4 combined to increase lung cancer risk in a case-control study in European American ever-smokers (n = 860). However, these genes are involved in the pharmacology of both nicotine, through which they alter smoking behaviours, and carcinogenic nitrosamines. Herein, we separated participants by CYP2B6 genotype into a high- vs. low-risk group (*1/*1 + *1/*6 vs. *6/*6). Odds ratios estimated …
Paracrine Sonic Hedgehog Signalling By Prostate Cancer Cells Induces Osteoblast Differentiation, Samantha M Zunich, Taneka Douglas, Maria Valdovinos, Tiffany Chang
Paracrine Sonic Hedgehog Signalling By Prostate Cancer Cells Induces Osteoblast Differentiation, Samantha M Zunich, Taneka Douglas, Maria Valdovinos, Tiffany Chang
Dartmouth Scholarship
Sonic hedgehog (Shh) and components of its signalling pathway have been identified in human prostate carcinoma and increased levels of their expression appear to correlate with disease progression and metastasis. The mechanism through which Shh signalling could promote metastasis in bone, the most common site for prostate carcinoma metastasis, has not yet been investigated. The present study determined the effect of Shh signalling between prostate cancer cells and pre-osteoblasts on osteoblast differentiation, a requisite process for new bone formation that characterizes prostate carcinoma metastasis.
Transactivation Of The Moloney Murine Leukemia Virus And T-Cell Receptor Beta-Chain Enhancers By Cbf And Ets Requires Intact Binding Sites For Both Proteins., Wanwen Sun, Barbara J. Graves, Nancy A. Speck
Transactivation Of The Moloney Murine Leukemia Virus And T-Cell Receptor Beta-Chain Enhancers By Cbf And Ets Requires Intact Binding Sites For Both Proteins., Wanwen Sun, Barbara J. Graves, Nancy A. Speck
Dartmouth Scholarship
The Moloney murine leukemia virus (Mo-MLV) enhancer contains binding sites (LVb and LVc) for the ets gene family of proteins and a core site that binds the polyomavirus enhancer-binding protein 2/core-binding factor (cbf) family of proteins. The LVb and core sites in the Mo-MLV enhancer contribute to its constitutive activity in T cells. All three binding sites (LVb, LVc, and core) are required for phorbol ester inducibility of the Mo-MLV enhancer. Adjacent binding sites for the ets and cbf proteins likewise constitute a phorbol ester response element within the human T-cell receptor beta-chain (TCR beta) enhancer and contribute to constitutive …
The Amino-Terminal Functions Of The Simian Virus 40 Large T Antigen Are Required To Overcome Wild-Type P53-Mediated Growth Arrest Of Cells., Robin S. Quartin, Charles N. Cole, James M. Pipas, Arnold J. Levine
The Amino-Terminal Functions Of The Simian Virus 40 Large T Antigen Are Required To Overcome Wild-Type P53-Mediated Growth Arrest Of Cells., Robin S. Quartin, Charles N. Cole, James M. Pipas, Arnold J. Levine
Dartmouth Scholarship
High levels of the p53 tumor suppressor protein can block progression through the cell cycle. A model system for the study of the mechanism of action of wild-type p53 is a cell line (T64-7B) derived from rat embryo fibroblasts transformed by activated ras and a temperature-sensitive murine p53 gene. At 37 to 39 degrees C, the murine p53 protein is in a mutant conformation and the cells actively divide, whereas at 32 degrees C, the protein has a wild-type conformation and the cells arrest in the G1 phase of the cell cycle. Wild-type simian virus 40 large T antigen and …
Cooperative Binding Of Ets-1 And Core Binding Factor To Dna., David Wotton, Jacques Ghysdael, Shuwen Wang, Nancy A. Speck, Michael J. Owen
Cooperative Binding Of Ets-1 And Core Binding Factor To Dna., David Wotton, Jacques Ghysdael, Shuwen Wang, Nancy A. Speck, Michael J. Owen
Dartmouth Scholarship
Two phorbol ester-inducible elements (beta E2 and beta E3) within the human T-cell receptor beta gene enhancer each contain consensus binding sites for the Ets and core binding factor (CBF) transcription factor families. Recombinant Ets-1 and purified CBF bound individually to beta E2 and beta E3, in which the Ets and core sites are directly adjacent. In this report, we show that CBF and Ets-1 bind together to beta E2 and beta E3 and that Ets-1-CBF-DNA complexes are favored over the binding of either protein alone to beta E2. Formation of Ets-1-CBF-DNA complexes increased the affinity of Ets-1-DNA interactions and …
Indistinguishable Nuclear Factor Binding To Functional Core Sites Of The T-Cell Receptor Delta And Murine Leukemia Virus Enhancers., Juan M. Redondo, Jeffrey L. Pfohl, Cristina Hernandez-Munain, Shuwen Wang, Nancy A. Speck, Michael S. Krangel
Indistinguishable Nuclear Factor Binding To Functional Core Sites Of The T-Cell Receptor Delta And Murine Leukemia Virus Enhancers., Juan M. Redondo, Jeffrey L. Pfohl, Cristina Hernandez-Munain, Shuwen Wang, Nancy A. Speck, Michael S. Krangel
Dartmouth Scholarship
We have previously shown that the delta E3 site is an essential element for transcriptional activation by the human T-cell receptor (TCR) delta enhancer and identified two factors, NF-delta E3A and NF-delta E3C, that bound to overlapping core (TGTGGTTT) and E-box motifs within delta E3. In this study, we show that protein binding to the core motif is necessary but not sufficient for transcriptional activation by the delta E3 element. In contrast, protein binding to the E-box motif does not contribute significantly to enhancer activity. A similar core motif present within the enhancers of T-cell-tropic murine retroviruses has been shown …
Purification Of Core-Binding Factor, A Protein That Binds The Conserved Core Site In Murine Leukemia Virus Enhancers., Shuwen W. Wang, Nancy A. Speck
Purification Of Core-Binding Factor, A Protein That Binds The Conserved Core Site In Murine Leukemia Virus Enhancers., Shuwen W. Wang, Nancy A. Speck
Dartmouth Scholarship
The Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major genetic determinant of the thymic disease specificity of the Moloney virus genetically maps to two protein binding sites in the Moloney virus enhancer, the leukemia virus factor b site and the adjacent core site. Point mutations introduced into either of these sites significantly shifts the disease specificity of the Moloney virus from thymic leukemia to erythroleukemia (N. A. Speck, B. Renjifo, E. Golemis, T. Frederickson, J. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We have purified several polypeptides that bind to the core site …
Identification Of A Complex Associated With Processing And Polyadenylation In Vitro Of Herpes Simplex Virus Type 1 Thymidine Kinase Precursor Rna., Fang Zhang, Charles N. Cole
Identification Of A Complex Associated With Processing And Polyadenylation In Vitro Of Herpes Simplex Virus Type 1 Thymidine Kinase Precursor Rna., Fang Zhang, Charles N. Cole
Dartmouth Scholarship
Cleavage and polyadenylation of substrate RNAs containing the herpes simplex virus type 1 (HSV-1) thymidine kinase (tk) gene polyadenylation signal region were examined in HeLa cell nuclear extract. 3'-End RNA processing was accurate and efficient and required ATP and Mg2+. Cleavage, but not polyadenylation, occurred in the presence of EDTA or when ATP was replaced with 3' dATP (cordycepin) or AMP(CH2)PP, a nonhydrolyzable analog of ATP. Processing in vitro and in vivo showed the same signal element requirements: a series of substrates containing linker scanning, internal deletion, and small insertion mutations was processed with the same relative efficiencies and at …