Medicine and Health Sciences Commons^™

Immune Evasion By Rabies Viruses Through The Maintenance Of Blood-Brain Barrier Integrity., Anirban Roy, Douglas C. Hooper

Department of Cancer Biology Faculty Papers

The attenuated rabies virus (RV) strain Challenge Virus Standard (CVS)-F3 and a highly pathogenic strain associated with the silver-haired bats (SHBRV) can both be cleared from the central nervous system (CNS) tissues by appropriate antiviral immune mechanisms if the effectors are provided access across the blood-brain barrier (BBB). In the case of SHBRV infection, antiviral immunity develops normally in the periphery but fails to open the BBB, generally resulting in a lethal outcome. To determine whether or not an absence in the CNS targeted immune response is associated with the infection with other pathogenic RV strains, we have assessed the …

Nerve Growth Factor Regulation Of Cyclin D1 In Pc12 Cells Through A P21ras Extracellular Signal-Regulated Kinase Pathway Requires Cooperative Interactions Between Sp1 And Nuclear Factor-Kappab., Francesco Marampon, Mathew C Casimiro, Maofu Fu, Michael J Powell, Vladimir M Popov, Jaime Lindsay, Bianca M Zani, Carmela Ciccarelli, Genichi Watanabe, Richard J Lee, Richard G Pestell

Department of Cancer Biology Faculty Papers

The PC12 pheochromocytoma cell line responds to nerve growth factor (NGF) by exiting from the cell cycle and differentiating to induce extending neurites. Cyclin D1 is an important regulator of G1/S phase cell cycle progression, and it is known to play a role in myocyte differentiation in cultured cells. Herein, NGF induced cyclin D1 promoter, mRNA, and protein expression via the p21(RAS) pathway. Antisense- or small interfering RNA to cyclin D1 abolished NGF-mediated neurite outgrowth, demonstrating the essential role of cyclin D1 in NGF-mediated differentiation. Expression vectors encoding mutants of the Ras/mitogen-activated protein kinase pathway, and chemical inhibitors, demonstrated NGF …

Transcription Factor Signal Transducer And Activator Of Transcription 5 Promotes Growth Of Human Prostate Cancer Cells In Vivo, Ayush Dagbadorj, Robert A. Kirken, Benjamin Leiby, James Karras, Marja T. Nevalainen

Department of Cancer Biology Faculty Papers

Purpose: Stat5a/b is the key mediator of prolactin (Prl) effects in prostate cancer cells via activation of Jak2. Prl is locally produced growth factor in human prostate cancer. Prl protein expression and constitutive activation of Stat5a/b are associated with high histological grade of clinical prostate cancer. Moreover, activation of Stat5a/b in primary prostate cancer predicts early disease recurrence. Here, we inhibited Stat5a/b by several different methodological approaches. Our goal was to establish a proof-of-principle that Stat5a/b is critical for prostate cancer cell viability in vitro and for prostate tumor growth in vivo.

Experimental Design: We inhibited Stat5a/b protein expression by …

Alternate Cyclin D1 Mrna Splicing Modulates P27Klp1 Binding And Cell Migration, Zhiping Li, Chenguang Wang, Xuanmao Jiao, Sanjay Katiyar, Mathew C. Casimiro, George C. Prendergast, Michael J. Powell, Richard G. Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 is an important cell cycle regulator but in cancer its overexpression also increases cellular migration mediated by p27^KlP1 stabilization and RhoA inhibition. Recently, a common polymorphism at the exon 4-intron 4 boundary of the human cyclin D1 gene within a splice donor region was associated with an altered risk of developing cancer. Altered RNA splicing caused by this polymorphism gives rise to a variant cyclin D1 isoform termed cyclin D1b, which has the same N-terminus as the canonical cyclin D1a isoform but a distinct C-terminus. In this study we show that these different isoforms have unique properties …

A Novel And Generalizable Organotypic Slice Platform To Evaluate Stem Cell Potential For Targeting Pediatric Brain Tumors., Shengwen Calvin Li, William Gunter Loudon

Department of Cancer Biology Faculty Papers

Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent …