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Discovery of novel molecular targets in cancer using bioinformatics
Title
Discovery of novel molecular targets in cancer using bioinformatics.
Creator
De Young, Maurice Phillip, V., Florida Atlantic University, Narayanan, Ramaswamy
Abstract/Description
The Cancer Genome Anatomy Project (CGAP) database of the National Cancer Institute contains thousands of expressed sequences, both known and novel, derived from diverse sets of normal, precancerous, and tumor cDNA libraries. This offers the possibility of using this database as a rational starting point for bioinformatics-based cancer gene discovery. Using the Digital Differential Display tool of the CGAP database, a hypothesis-driven gene discovery approach was undertaken to analyze...
Show moreThe Cancer Genome Anatomy Project (CGAP) database of the National Cancer Institute contains thousands of expressed sequences, both known and novel, derived from diverse sets of normal, precancerous, and tumor cDNA libraries. This offers the possibility of using this database as a rational starting point for bioinformatics-based cancer gene discovery. Using the Digital Differential Display tool of the CGAP database, a hypothesis-driven gene discovery approach was undertaken to analyze differential expression of various solid tumor types. Two hundred known genes and five hundred novel sequences were discovered to be differentially expressed, and a comprehensive database was established to facilitate identification of cancer diagnostic and therapeutic targets. To validate the use of bioinformatics in discovering genes with organ- and tumor-selectivity, novel ESTs predicted to be colon tumor-specific were analyzed further for expression specificity. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) analysis using matched sets of colon normal- and tumor-derived cDNAs identified one EST to be specifically expressed in the majority of colon tumors and normal small intestine. Due to this apparent specificity, the gene was termed Colon Carcinoma Related Gene (CCRG). Based on protein sequence analysis, CCRG belongs to a novel class of secreted factors. Another gene identified in this study showed homology to Single Minded 2 gene (SIM2). Involvement between SIM2 and cancer has not yet been reported. Isoform-specific expression of SIM2 short-form (SIM2-s) was seen in colon, pancreas, and prostate carcinomas but not in most normal tissues. Using a large collection of paraffin sections from colon, pancreas, and prostate tumor and normal tissues, elevated protein expression was seen in tumors compared to normal tissue specimens, demonstrating the diagnostic potential of SIM2-s. Antisense inhibition of SIM2-s expression in colon and pancreatic cancer cell lines caused inhibition of gene expression, growth inhibition, and apoptosis. Administration of SIM2-s antisense in nude mice caused inhibition of colon tumor growth without pronounced gross toxicity. Using GeneChipRTM technology, a gene expression profile indicative of apoptosis was observed in the colon cancer model. CCRG and SIM2-s offer both a diagnostic and therapeutic potential in select cancers and validate the use of bioinformatics approaches in the gene discovery paradigm.
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Date Issued
2003
PURL
http://purl.flvc.org/fau/fd/FADT12053
Subject Headings
Bioinformatics, Gene expression, Oncogenes
Format
Document (PDF)
Study of the Coupling Between Transcription and mRNA Processing Utilizing a Novel Bcl-x Mini-gene
Title
Study of the Coupling Between Transcription and mRNA Processing Utilizing a Novel Bcl-x Mini-gene.
Creator
Devanney, Sean C., Caputi, Massimo, Florida Atlantic University
Abstract/Description
The Bel family of genes are fundamental to the apoptotic mechanism. Bcl-x a member of this family, is alternatively spliced to create two main isoforms a long (Bcl-xL) and a short (Bcl-xS) variant. The long form exhibits anti-apoptotic activity, while the short form favors apoptosis. The proper balance of expression of these two isoforms is crucial for several developmental processes such as thymic selection and neural reshaping. A number of cancer types have been shown to over-express the...
Show moreThe Bel family of genes are fundamental to the apoptotic mechanism. Bcl-x a member of this family, is alternatively spliced to create two main isoforms a long (Bcl-xL) and a short (Bcl-xS) variant. The long form exhibits anti-apoptotic activity, while the short form favors apoptosis. The proper balance of expression of these two isoforms is crucial for several developmental processes such as thymic selection and neural reshaping. A number of cancer types have been shown to over-express the long form, thereby granting them some protection from apoptosis. To study the transcriptional and post-transcriptional mechanisms regulating gene expression, the Bcl-x gene has been utilized. A complex mini-gene construct has been create in order to monitor the effects that promoter sequences, 5'UTR and 3'UTR's have on mRNA splicing, RNA export, stability and translation. Abundant evidence exists indicating that RNA processing events such as transcription, splicing and export are coupled, yet the mechanisms and factors involved in regulating these processes are poorly understood. The mini-gene is identical to the endogenous gene with the exception of a deletion to the 50Kb intron and the addition of a tag to differentiate the mini-gene product from the endogenous mRNA and protein. This novel system allows for the study of transcriptional and post-transcriptional mechanisms regulating gene expression from RNA biogenesis on to the protein level.
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Date Issued
2007
PURL
http://purl.flvc.org/fau/fd/FA00000741
Subject Headings
Genetic transcription, Proteins--Synthesis, Messenger RNA, Gene expression, Oncogenes--Research
Format
Document (PDF)
Taurine protection of PC12 cells against endoplasmic reticulum stress induced by oxidative stress
Title
Taurine protection of PC12 cells against endoplasmic reticulum stress induced by oxidative stress.
Creator
Pan, Chunliu, Giraldo, Grace S., Prentice, Howard, Wu, Jang-Yen
Date Issued
2010-08-24
PURL
http://purl.flvc.org/fcla/dt/3327276
Subject Headings
Oxidative Stress, Oxidative Stress --drug effects, Oxidative Stress --physiology, Antioxidants --pharmacology, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-bcl-2, PC12 Cells --drug effects, Endoplasmic Reticulum --drug effects, Transcription Factor CHOP, Taurine
Format
Document (PDF)
Role of taurine in the central nervous system
Title
Role of taurine in the central nervous system.
Creator
Wu, Jang-Yen, Prentice, Howard
Date Issued
2010-08-24
PURL
http://purl.flvc.org/fau/fd/FADT3327262
Subject Headings
Central Nervous System --metabolism, Glutamic Acid --metabolism, Homeostasis --physiology, Neuroprotective Agents --metabolism, Neurotransmitter Agents --metabolism, Proto-Oncogene Proteins c-bcl-2 --metabolism, Receptors, Neurotransmitter --metabolism, Signal Transduction --physiology, Taurine, Taurine --metabolism, Neuroprotective Agents, Neurotransmitter Agents
Format
Document (PDF)