Cancer Genes, Tumor Suppressors, and Regulation of IGF1-R Gene Expression in Cancer

Author(s):  
Haim Werner ◽  
Zohar Attias-Geva ◽  
Itay Bentov ◽  
Rive Sarfstein ◽  
Hagit Schayek ◽  
...  
2005 ◽  
Vol 113 (S 1) ◽  
Author(s):  
O Zwermann ◽  
A Braun ◽  
E Lalli ◽  
F Beuschlein ◽  
M Reincke

2013 ◽  
Vol 40 (10) ◽  
pp. 1029 ◽  
Author(s):  
Aguida M. A. P. Morales ◽  
Jamie A. O'Rourke ◽  
Martijn van de Mortel ◽  
Katherine T. Scheider ◽  
Timothy J. Bancroft ◽  
...  

Rpp4 (Resistance to Phakopsora pachyrhizi 4) confers resistance to Phakopsora pachyrhizi Sydow, the causal agent of Asian soybean rust (ASR). By combining expression profiling and virus induced gene silencing (VIGS), we are developing a genetic framework for Rpp4-mediated resistance. We measured gene expression in mock-inoculated and P. pachyrhizi-infected leaves of resistant soybean accession PI459025B (Rpp4) and the susceptible cultivar (Williams 82) across a 12-day time course. Unexpectedly, two biphasic responses were identified. In the incompatible reaction, genes induced at 12 h after infection (hai) were not differentially expressed at 24 hai, but were induced at 72 hai. In contrast, genes repressed at 12 hai were not differentially expressed from 24 to 144 hai, but were repressed 216 hai and later. To differentiate between basal and resistance-gene (R-gene) mediated defence responses, we compared gene expression in Rpp4-silenced and empty vector-treated PI459025B plants 14 days after infection (dai) with P. pachyrhizi. This identified genes, including transcription factors, whose differential expression is dependent upon Rpp4. To identify differentially expressed genes conserved across multiple P. pachyrhizi resistance pathways, Rpp4 expression datasets were compared with microarray data previously generated for Rpp2 and Rpp3-mediated defence responses. Fourteen transcription factors common to all resistant and susceptible responses were identified, as well as fourteen transcription factors unique to R-gene-mediated resistance responses. These genes are targets for future P. pachyrhizi resistance research.


1993 ◽  
Vol 11 (1) ◽  
pp. 1-7 ◽  
Author(s):  
I M Adcock ◽  
M Peters ◽  
C Gelder ◽  
H Shirasaki ◽  
C R Brown ◽  
...  

ABSTRACT Substance P has several inflammatory effects on the airways mediated via neurokinin 1 receptors (NK1Rs) and, if released from sensory nerves, may amplify the chronic inflammation seen in asthma. Northern blot analysis of NK1R mRNA in lung showed a 52 ± 10% (s.e.m.; P<0·01) increase in mRNA in the asthmatic lung compared with non-asthmatic control tissue. NK1R mRNA was reduced by 84·5 ± 1·9% after incubation with dexamethasone (1 μm) for 3 h (P<0·01). In contrast, NK2R mRNA was unaltered in asthmatic lungs and dexamethasone treatment had no effect on the level of NK2R mRNA. These results suggest that chronic inflammation in asthma may result in increased NK1R gene expression and that this effect is reversed by glucocorticosteroids.


2021 ◽  
pp. 1-14
Author(s):  
Danbi Seo ◽  
Jungwook Roh ◽  
Yeonsoo Chae ◽  
Wanyeon Kim

Lung cancer accounts for a large proportion of cancer-related deaths worldwide. Personalized therapeutic medicine based on the genetic characteristics of non-small cell lung cancer (NSCLC) is a promising field, and discovering clinically applicable biomarkers of NSCLC is required. LINC00472 is a long non-coding RNA and has been recently suggested to be a biomarker of NSCLC, but little is known of its mechanism in NSCLC. Thus, the current study was performed to document changes in gene expression after LINC00472 overexpression in NSCLC cells. As a result of cell viability and migration assay, LINC00472 downregulated cell survival, proliferation, and motility. Transcriptome sequencing analysis showed 3,782 genes expression were changed in LINC00472 overexpressing cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed most genes were associated with intracellular metabolism. The PPP1R12B, RGS5, RBM5, RBL2, LDLR and PTPRM genes were upregulated by LINC00472 overexpression and these genes functioned as tumor suppressors in several cancers. In contrast, SPSB1, PCNA, CD24, CDK5, CDC25A, and EIF4EBP1 were downregulated by LINC00472, and they functioned as oncogenes in various cancers. Consequently, the function of LINC00472 in tumorigenesis might be related to changes in the expressions of other oncogenes and tumor suppressors.


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3812
Author(s):  
Jan Willem Bruggeman ◽  
Naoko Irie ◽  
Paul Lodder ◽  
Ans M. M. van Pelt ◽  
Jan Koster ◽  
...  

We have recently described a class of 756 genes that are widely expressed in cancers, but are normally restricted to adult germ cells, referred to as germ cell cancer genes (GC genes). We hypothesized that carcinogenesis involves the reactivation of biomolecular processes and regulatory mechanisms that, under normal circumstances, are restricted to germline development. This would imply that cancer cells share gene expression profiles with primordial germ cells (PGCs). We therefore compared the transcriptomes of human PGCs (hPGCs) and PGC-like cells (PGCLCs) with 17,382 samples from 54 healthy somatic tissues (GTEx) and 11,003 samples from 33 tumor types (TCGA), and identified 672 GC genes, expanding the known GC gene pool by 387 genes (51%). We found that GC genes are expressed in clusters that are often expressed in multiple tumor types. Moreover, the amount of GC gene expression correlates with poor survival in patients with lung adenocarcinoma. As GC genes specific to the embryonic germline are not expressed in any adult tissue, targeting these in cancer treatment may result in fewer side effects than targeting conventional cancer/testis (CT) or GC genes and may preserve fertility. We anticipate that our extended GC dataset enables improved understanding of tumor development and may provide multiple novel targets for cancer treatment development.


Nature ◽  
2005 ◽  
Vol 435 (7045) ◽  
pp. 1122-1125 ◽  
Author(s):  
Keyu Gu ◽  
Bing Yang ◽  
Dongsheng Tian ◽  
Lifang Wu ◽  
Dongjiang Wang ◽  
...  

2013 ◽  
Vol 40 (7) ◽  
pp. 4173-4180 ◽  
Author(s):  
Ioannis Kafantaris ◽  
Pasqualina Woodrow ◽  
Petronia Carillo
Keyword(s):  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonio Colaprico ◽  
Catharina Olsen ◽  
Matthew H. Bailey ◽  
Gabriel J. Odom ◽  
Thilde Terkelsen ◽  
...  

AbstractCancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. With them, we classify cancer driver genes, unveiling their roles in cancer mechanisms. To this end, we present Moonlight, a tool that incorporates multiple -omics data to identify critical cancer driver genes. With Moonlight, we analyze 8000+ tumor samples from 18 cancer types, discovering 3310 oncogenic mediators, 151 having dual roles. By incorporating additional data (amplification, mutation, DNA methylation, chromatin accessibility), we reveal 1000+ cancer driver genes, corroborating known molecular mechanisms. Additionally, we confirm critical cancer driver genes by analysing cell-line datasets. We discover inactivation of tumor suppressors in intron regions and that tissue type and subtype indicate dual role status. These findings help explain tumor heterogeneity and could guide therapeutic decisions.


1995 ◽  
Vol 15 (7) ◽  
pp. 3516-3522 ◽  
Author(s):  
H Werner ◽  
Z Shen-Orr ◽  
F J Rauscher ◽  
J F Morris ◽  
C T Roberts ◽  
...  

We have investigated the regulation of the insulin-like growth factor I receptor (IGF-I-R) gene promoter by the Wilms' tumor suppressor WT1 in intact cells. The levels of endogenous IGF-I-R mRNA and the activity of IGF-I-R gene promoter fragments in luciferase reporter constructs were found to be significantly higher in G401 cells (a Wilms' tumor-derived cell line lacking detectable WT1 mRNA) than in 293 cells (a human embryonic kidney cell line which expresses significant levels of WT1 mRNA). To study whether WT1 could suppress the expression of the endogenous IGF-I-R gene, WT1-negative G401 cells were stably transfected with a WT1 expression vector. Expression of WT1 mRNA in G401 cells resulted in a significant decrease in the rate of cellular proliferation, which was associated with a reduction in the levels of IGF-I-R mRNA, promoter activity, and ligand binding and with a reduction in IGF-I-stimulated cellular proliferation, thymidine incorporation, and anchorage-independent growth. These data suggest that a major aspect of the action of the WT1 tumor suppressor is the repression of IGF-I-R gene expression.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Bi-Qing Li ◽  
Jin You ◽  
Lei Chen ◽  
Jian Zhang ◽  
Ning Zhang ◽  
...  

Lung cancer is one of the leading causes of cancer mortality worldwide. The main types of lung cancer are small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC). In this work, a computational method was proposed for identifying lung-cancer-related genes with a shortest path approach in a protein-protein interaction (PPI) network. Based on the PPI data from STRING, a weighted PPI network was constructed. 54 NSCLC- and 84 SCLC-related genes were retrieved from associated KEGG pathways. Then the shortest paths between each pair of these 54 NSCLC genes and 84 SCLC genes were obtained with Dijkstra’s algorithm. Finally, all the genes on the shortest paths were extracted, and 25 and 38 shortest genes with a permutationPvalue less than 0.05 for NSCLC and SCLC were selected for further analysis. Some of the shortest path genes have been reported to be related to lung cancer. Intriguingly, the candidate genes we identified from the PPI network contained more cancer genes than those identified from the gene expression profiles. Furthermore, these genes possessed more functional similarity with the known cancer genes than those identified from the gene expression profiles. This study proved the efficiency of the proposed method and showed promising results.


Sign in / Sign up

Export Citation Format

Share Document