|Author||Unoki M, Nakamura Y.|
|Title||Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway.|
Defects in PTEN, a tumor suppressor, have been found in cancers arising in a variety of human tissues. To elucidate the tumor-suppressive function of this gene, we have been analysing expression profiles of cancer cells after introduction of exogenous PTEN. Those experiments identified 99 candidate genes that were transcriptionally transactivated. Among them, we report here the further analyses of eight genes, EGR2/Krox-20, BPOZ, APS, HCLS1/HS1, DUSP1/MKP1, NDRG1/Drg1/RTP, NFIL3/E4BP4, and a novel gene (PINK1, PTEN-induced putative kinase). Expression of six of them (PINK1, EGR2, HCLS1, DUSP1, BPOZ, and NFIL3) was decreased in ovarian tumors compared with corresponding normal tissues. Colony-formation assays using plasmid clones designed to express each gene indicated that EGR2 and BPOZ were able to suppress growth of cancer cells significantly; in particular, cancer-cell lines stably expressing BPOZ grew more slowly than control cells containing mock vector. Flow cytometry suggested that over-expression of BPOZ inhibited progression of the cell cycle at the G(1)/S transition. Anti-sense oligonucleotides for BPOZ or EGR2 effectively inhibited their expression, and cell growth was accelerated. Therefore both genes appear to be novel candidates as mediators of the PTEN growth-suppressive signaling pathway.
|MeSH||Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport* Adult Amino Acid Sequence Ankyrin Repeat Basic-Leucine Zipper Transcription Factors Blood Proteins / genetics Blood Proteins / physiology Cell Cycle / genetics Cell Cycle Proteins / genetics Cell Cycle Proteins / physiology Cell Division / genetics DNA-Binding Proteins / genetics DNA-Binding Proteins / physiology Dual Specificity Phosphatase 1 Early Growth Response Protein 2 Expressed Sequence Tags Female G-Box Binding Factors Gene Expression Profiling Genes, Tumor Suppressor* Humans Immediate-Early Proteins / genetics Immediate-Early Proteins / physiology Intracellular Signaling Peptides and Proteins Male Molecular Sequence Data Neoplasm Proteins / biosynthesis Neoplasm Proteins / genetics Neoplasm Proteins / pharmacology* Neoplasm Proteins / physiology* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / physiology Oligodeoxyribonucleotides, Antisense / pharmacology Ovarian Neoplasms / genetics Ovarian Neoplasms / pathology* PTEN Phosphohydrolase Phosphoprotein Phosphatases* Phosphoric Monoester Hydrolases / genetics Phosphoric Monoester Hydrolases / physiology* Protein Kinases / genetics Protein Kinases / physiology Protein Phosphatase 1 Protein Structure, Tertiary Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / physiology Proteins / genetics Proteins / physiology* RNA Splicing Recombinant Fusion Proteins / physiology Repressor Proteins* Sequence Alignment Signal Transduction / genetics* Subcellular Fractions / metabolism Transcription Factors / genetics Transcription Factors / physiology Transcriptional Activation Transfection Tumor Cells, Cultured / metabolism Tumor Cells, Cultured / pathology Tumor Stem Cell Assay Tumor Suppressor Proteins*|
|Human and Animal Cells||Sawano(RCB1152)|