IG20 splice variants therapeutics for cancer

Details IG20 splice variants therapeutics for cancer IG20 splice variants therapeutics for cancer

2011-03-22

2011-03-22

Chong, Kimberly (Department: 1635)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C536S024310, C536S024100, C435S006120, C435S325000, C435S375000, C514S04400A

Reexamination Certificate

active

07910723

ABSTRACT:
Methods and compositions inhibit the growth of cancer cells by selectively down-regulating the expression of an IG20 splice variant including MADD. Specific knock-down of MADD splice variant resulted in the apoptosis of cancer cells. Interfering RNAs including small hairpin RNAs (shRNA) to down-regulate MADD expression in vivo are disclosed. Inhibition of MADD phosphorylation by Akt results in activation of cancer cell death. Down-regulation of MADD expression results in switching to apoptotic mode due to lack of MAPK activation upon TNF-α-based induction.

REFERENCES:
patent: 2003/0162734 (2003-08-01), Miller et al.
patent: 2007/0031844 (2007-02-01), Khvorova et al.
patent: 2008/0233645 (2008-09-01), Prabhakar
patent: WO 2005/037303 (2005-04-01), None
patent: WO 2007/084954 (2007-07-01), None
Thompson et al. Applications of antisense and siRNAs during preclinical drug development. DDT Vo. 7, No. 17, 2002.
Efimova et al., “Differential Effects of IG20 and Its Splice Isoform, DENN-SV, on Cell Proliferation and Apoptosis,”FASEB Jrnl., 16:5 A1083 (2002).
Hilger et al., “The Ras-Raf-MEK-ERK Pathway in the Treatment of Cancer,”Onkologie, 25 (6), 511-518 (2002).
International Search Report issued in PCT/US2004/030986 (2005).
Al-Zoubi et al., “Contrasting Effects of IG20 and Its Splice Isoforms, MADD and DENN-SV, on Tumor Necrosis Factor alpha-induced Apoptosis and Activation of Caspase-8 and -3,”The Journal of Biological Chemistry, 276 (50): 47202-47211 (2001).
Antignani et al., “How do Bax and Bak lead to permeabilization of the outer mitochondrial membrane?,”Current Opinion in Cell Biology, 18: 685-689 (2006).
Barber et al., “Membrane Translocation of P-Rex1 is Mediated by G Protein Betagamma Subunits and Phosphoinositide 3-Kinase,”The Journal of Biological Chemistry, 282 (41): 29967-29976 (2007).
Bhaskar et al., “The Two TORCS and Akt,”Developmental Cell, 12: 487-502 (2007).
Brinkman et al., “Engagement of Tumor Necrosis Factor (TNF) Receptor 1 Leads to ATF-2-and p38 Mitogen-activated Protein Kinase-dependent TNF-alpha Gene Expression,”The Journal of Biological Chemistry, 274 (43): 30882-30886 (1999).
Brown et al., “MADD is highly homologous to a Rab3 guanine-nucleotide exchange protein (Rab3-GEP),”Curr. Biol., 8 (6): R191 (1998).
Brunet et al., “Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor,”Cell, 96 (43): 857-868 (1999).
Chow et al., “DENN, a novel human gene differentially expressed in normal and neoplastic cells,”DNA Sequence—The Journal of Sequencing and Mapping, 6: 263-273 (1996).
Chow et al., “The human DENN gene: genomic organization, alternative splicing, and localization to chromosome 11p. 11.21-p. 11.22,”Genome, 41: 543-552 (1998).
Cuevas et al., “Role of mitogen-activated protein kinase kinase kinases in signal integration,”Oncogene, 26: 3159-3171 (2007).
Datta et al., “Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery,”Cell, 91: 231-241 (1997).
De Cesare et al., “Rsk-2 activity is necessary for epidermal growth factor-induced phosphorylation of CREB protein and transcription ofc-fosgene,”Proc. Natl. Acad. Sci., 95: 12202-12207 (1998).
Del Villar et al., “Down Regulation of DENN/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer's disease brain and hippocampal neurons,”PNAS, 101 (12): 4210-4215 (2004).
Dhillon et al., “MAP kinase signaling pathways in cancer,”Oncogene, 26: 3279-3290 (2007).
Dohi et al., “Comparmentalized Phosphorylation of IAP by Protein Kinase A Regulates Cytoprotection,”Molecular Cell, 27: 17-28 (2007).
Du et al., “Smac, a Mitochondrial Protein that Promotes Cytochrome c-Dependent Caspase Activation by Eliminating IAP Inhibition,”Cell, 102: 33-42 (2000).
Efimova et al., “IG20, a MADD Splice Variant, Increases Cell Susceptibility to gamma-Irradiation and Induces Soluble Mediators That Suppress Tumor Cell Growth,”Cancer Research, 63: 8768-8776 (2003).
Efimova et al., “IG20, in contract to DENN-SV, (MADD Splice Variants) suppresses tumor cell survival, and enhances their susceptibility to apoptosis and cancer drugs,”Oncogene, 23: 1076-1087 (2004).
Garcia-Blanco et al., “Alternative splicing in disease and therapy,”Nature Biotechnology, 22 (5): 535-546 (2004).
Gardai et al., “Phosphorylation of Bax Ser184 by Akt Regulates Its Activity and Apoptosis in Neutrophils,”The Journal of Biological Chemistry, 279 (20): 21085-21095 (2004).
Goto et al., “A Novel Human Insulinoma-associated cDNA, IA-1, Encodes a Protein with “Zinc-finger” DNA-binding Motifs,”The Journal of Biological Chemistry, 267 (21): 15252-15257 (1992).
Herdegen et al., “Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins,”Brain Research Reviews, 28: 370-490 (1998).
Iwasaki et al., “The Rab3 GDP/GTP exchange factor homolog AEX-3 has a dual function in synaptic transmission,”The EMBO Journal, 19 (17): 4806-4816 (2000).
Kalnina et al., “Alterations of Pre-mRNA Splicing in Cancer,”Genes, Chromosomes&Cancer, 42: 342-357 (2005).
Kozielski et al., “A model of the microtubule-kinesin complex based on electron cryomicroscopy and X-ray crystallography,”Current Biology, 8: 191-198 (1998).
Lee et al., “Interaction of HCV core protein with 14-3-3xi protein releases Bax to activate apoptosis,”Biochemical and Biophysical Research Communications, 352: 756-762 (2007).
Levivier et al., “uDENN, DENN, and dDENN: Indissociable Domains in Rab and MAP Kinasis Signaling Pathways,”Biochemical and Biophysical Research Communications, 287: 688-695 (2001).
Li et al., “Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates and Apoptotic Protease Cascade,”Cell, 91: 479-489 (1997).
Li et al., “p53 regulates mitochondrial membrane potential through reactive oxygen species and induces cytochromec-independent apoptosis blocked by Bcl-2,”The EMBO Journal, 18 (21): 6027-6036 (1999).
Li et al., “Phosphorylation by Protein Kinase CK2: A Signaling Switch for the Caspase-Inhibiting Protein ARC,”Molecular Cell, 10: 247-258 (2002).
Lim et al., “Induction of Marked Apoptosis in Mammalian Cancer Cell Lines by Antisense DNA Treatment to Abolish Expression of DENN (Differently Expressed in Normal and Neoplastic Cells),”Molecular Carcinogenesis, 35: 110-126 (2002).
Lim et al., “Antisense Abrogation of DENN Expression Induces Apoptosis of Leukemia Cells in Vitro, Causes Tumor Regression In Vivo and Alters the Transcription of Genes Involved in Apoptosis and the Cell Cycle,”Int. J. Cancer, 109: 24-37 (2004).
Liu et al., “Dissection of TNF Receptor 1 Effector Functions: JNK Activation Is Not Linked to Apoptosis While NF-kappaB Activation Prevents Cell Death,”Cell, 87: 565-576 (1996).
LoPiccolo et al., “Targeting Akt in cancer therapy,”Anti-Cancer Drugs, 18: 861-874 (2007).
Manning et al., “AKT/PKB Signaling: Navigating Downstream,”Cell, 129: 1261-1274 (2007).
Mayo et al., “A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus,”PNAS, 98 (20): 11598-11603 (2001).
Micheau et al., “Induction of TNF Receptor I-Mediated Apoptosis via Two Sequential Signaling Complexes,”Cell, 114: 181-190 (2003).
Mulherkar et al., “MADD/DENN splice variant of theIG20 geneis necessary and sufficient for cancer cell survival,”Oncogene, 25: 6252-6261 (2006).
Mulherkar et al., “MADD/DENN Splice Variant of the IG20 Gene Is a Negative Regulator of Caspase-8 Activation,”The Journa

Affiliated with

Also associated with

Rating

IG20 splice variants therapeutics for cancer does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with IG20 splice variants therapeutics for cancer, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and IG20 splice variants therapeutics for cancer will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2765141