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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3-4
pubmed:dateCreated
2004-11-23
pubmed:abstractText
We analyzed the differential gene expression in the pancreatic cancer cell line NP-18 upon induction of apoptosis caused by cyclin-dependent kinase inhibition triggered by either overexpression of the tumor suppressor gene p16(INK4A)using an adenoviral construction or incubation with the chemical inhibitors, roscovitine or olomoucine. Screening was performed using cDNA arrays from Clontech that allowed the determination of the expression of 1,176 genes specifically related with cancer. The analysis was carried out using the Atlas Image 2.01 (Clontech) and GeneSpring 4.2 (Silicon Genetics) softwares. Among the differentially expressed genes, we chose for further validation histone deacetylase 1 (HDAC1), von Hippel Lindau and decorin as upregulated genes, and Sp1, hypoxia-inducible factor-1 alpha and DNA primase as downregulated genes. The changes in the expression of these genes to mRNA were validated by quantitative RT-PCR and the final translation into protein by Western blot analysis. Inhibition of HDAC activity, Sp1 binding and DNA primase expression led to an increase in the level of apoptosis, both in parental cells and in doxorubicin-resistant cells. Therefore, these proteins could constitute possible targets to develop modulators in cancer chemotherapy that would increase or restore apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor..., http://linkedlifedata.com/resource/pubmed/chemical/DCN protein, human, http://linkedlifedata.com/resource/pubmed/chemical/DNA Primase, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Decorin, http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins, http://linkedlifedata.com/resource/pubmed/chemical/HDAC1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 1, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases, http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha..., http://linkedlifedata.com/resource/pubmed/chemical/Kinetin, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Proteoglycans, http://linkedlifedata.com/resource/pubmed/chemical/Purines, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases, http://linkedlifedata.com/resource/pubmed/chemical/VHL protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Von Hippel-Lindau Tumor Suppressor..., http://linkedlifedata.com/resource/pubmed/chemical/olomoucine, http://linkedlifedata.com/resource/pubmed/chemical/roscovitine
pubmed:status
MEDLINE
pubmed:issn
0030-2414
pubmed:author
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
277-90
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15557790-Humans, pubmed-meshheading:15557790-Pancreatic Neoplasms, pubmed-meshheading:15557790-Purines, pubmed-meshheading:15557790-Antineoplastic Agents, pubmed-meshheading:15557790-Adenoviridae, pubmed-meshheading:15557790-Extracellular Matrix Proteins, pubmed-meshheading:15557790-Nuclear Proteins, pubmed-meshheading:15557790-Tumor Markers, Biological, pubmed-meshheading:15557790-Cell Line, Tumor, pubmed-meshheading:15557790-Kinetin, pubmed-meshheading:15557790-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15557790-DNA-Binding Proteins, pubmed-meshheading:15557790-Protein Kinase Inhibitors, pubmed-meshheading:15557790-Proteoglycans, pubmed-meshheading:15557790-Down-Regulation, pubmed-meshheading:15557790-Histone Deacetylases, pubmed-meshheading:15557790-Apoptosis, pubmed-meshheading:15557790-Transcription Factors, pubmed-meshheading:15557790-Genetic Vectors, pubmed-meshheading:15557790-DNA Primase, pubmed-meshheading:15557790-Gene Expression Profiling, pubmed-meshheading:15557790-Ubiquitin-Protein Ligases, pubmed-meshheading:15557790-Tumor Suppressor Proteins, pubmed-meshheading:15557790-Blotting, Western, pubmed-meshheading:15557790-Up-Regulation, pubmed-meshheading:15557790-Decorin, pubmed-meshheading:15557790-Hypoxia-Inducible Factor 1, pubmed-meshheading:15557790-Hypoxia-Inducible Factor 1, alpha Subunit, pubmed-meshheading:15557790-Cyclin-Dependent Kinase Inhibitor p16
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