scholarly journals Dose-response relationships in gene expression profiles in a harbor seal B lymphoma cell line exposed to 17α-ethinyl estradiol

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Christine Kleinert ◽  
Matthieu Blanchet ◽  
François Gagné ◽  
Michel Fournier

The determination of changes in gene expression profiles with xenobiotic dose will allow identifying biomarkers and modes of toxicant action. The harbor seal (Phoca vitulina) 11B7501 B lymphoma cell line was exposed to 1, 10, 100, 1000, 10,000, or 25,000 μg/L 17α-ethinyl estradiol (EE2, the active compound of the contraceptive pill) for 24 h. Following exposure, RNA was extracted and transformed into cDNA. Transcript expression in exposed vs. control lymphocytes was analyzed via RT-qPCR to identify genes with altered expression. Our analysis indicates that gene expression for all but the reference gene varied with dose, suggesting that different doses induce distinct physiological responses. These findings demonstrate that RT-qPCR could be used to identify immunotoxicity and relative dose in harbor seal leukocytes.


2017 ◽  
Vol 118 (1-2) ◽  
pp. 237-247 ◽  
Author(s):  
Christine Kleinert ◽  
Emilie Lacaze ◽  
Méryl Mounier ◽  
Sylvain De Guise ◽  
Michel Fournier


2021 ◽  
Author(s):  
Zeynep Ates-Alagoz ◽  
Mehmet Murat Kisla ◽  
Fikriye Zengin Karadayi ◽  
Sercan Baran ◽  
Tuğba Somay Doğan ◽  
...  

Several indole-thiazolidinedione derivatives (9–24) were designed and synthesized as CDK6 inhibitors, and their anticancer activity was probed on the MCF-7 cell line and the effects on gene expression profiles were elucidated.



2002 ◽  
Vol 277 (32) ◽  
pp. 29283-29293 ◽  
Author(s):  
Martin Stacey ◽  
Gin-Wen Chang ◽  
Stephanie L. Sanos ◽  
Laura R. Chittenden ◽  
Lisa Stubbs ◽  
...  


2019 ◽  
Author(s):  
Qiong Zhang ◽  
Mei Luo ◽  
Chun-Jie Liu ◽  
An-Yuan Guo

AbstractCancer cell lines (CCLs) as important model systems play critical roles in cancer researches. The misidentification and contamination of CCLs are serious problems, leading to unreliable results and waste of resources. Current methods for CCL authentication are mainly based on the CCL-specific genetic polymorphisms, whereas no method is available for CCL authentication using gene expression profiles. Here, we developed a novel method and homonymic web server (CCLA, Cancer Cell Line Authentication, http://bioinfo.life.hust.edu.cn/web/CCLA/) to authenticate 1,291 human CCLs of 28 tissues using gene expression profiles. CCLA curated CCL-specific gene signatures and employed machine learning methods to measure overall similarities and distances between the query sample and each reference CCL. CCLA showed an excellent speed advantage and high accuracy with a top 1 accuracy of 96.58% or 92.15% (top 3 accuracy of 100% or 95.11%) for microarray or RNA-Seq validation data (719 samples, 461 CCLs), respectively. To the best of our knowledge, CCLA is the first approach to authenticate CCLs based on gene expression. Users can freely and conveniently authenticate CCLs using gene expression profiles or NCBI GEO accession on CCLA website.



2004 ◽  
Vol 14 (5) ◽  
pp. 984-997 ◽  
Author(s):  
J. Q. Cui ◽  
Y. F. Shi ◽  
H. J. Zhou ◽  
J. Q. Li

The purpose of this study is to investigate changes of gene expression profiles in hydatidiform moles (HM) and choriocarcinoma and to explore causes of trophoblastic hyperplasia. Using cDNA microarray, 4096 genes were analyzed in two pairs of the tissues of HM versus normal villi and in two pairs of normal primary culture trophoblasts versus JAR cell line of choriocarcinoma. The expressions of two genes in normal villi and HM, as well as in JAR and JEG-3, were examined with the help of immunohistochemistry, immunoblot, and reverse transcriptase-polymerase chain reaction in order to confirm the findings of cDNA microarray. Twenty-four genes were upregulated and 65 genes were downregulated in all HM. Four hundred thirty-three genes were upregulated and 380 genes were downregulated in JAR. Forty-six genes were upregulated in both HM and choriocarcinoma, whereas 13 genes were downregulated. Genes associated with the inhibition of cell proliferation were significantly downregulated, whereas genes associated with cell proliferation, malignant transformation, metastasis, and drug resistance were upregulated. Thymidine kinase-1 (TK-1) and small subunit ribonucleotide reductase (RRM-2) were overexpressed in HM, JAR, and JEG-3. The expressions of TK-1 and RRM-2 in moles were positively correlated with proliferative index of trophoblasts. Our results suggest that altered expression of genes exist in HM and choriocarcinoma. Trophoblastic hyperplasia may be involved in the overexpression of DNA synthetic enzymes.



2019 ◽  
Vol 26 (5) ◽  
pp. 348-356
Author(s):  
Xiu Li Feng ◽  
Yang Zheng ◽  
Shan Shan Hao ◽  
Guang Fang Zhou ◽  
Pu Yan Chen

Background: The Bursa of Fabricius is an acknowledged central humoral immune organ unique to birds, which provides an ideal research model on the immature B cell development. Objective: In this article, our motivation is to study the role on sIgM and establish the molecular basis and functional processes of Bursal Hexapeptide (BHP) in avian immature B cells DT40 cell lines. Methods: In this article, we detected the expressions of sIgM mRNA with qPCR in DT40 cells with BHP treatment, and investigated the gene expression profiles of BHP-treated DT40 cells, employing microarray analyses. Also, to validate the differentially expressed genes, we performed KEGG pathway and Gene Ontology analysis in the BHP-treated DT40 cells. Finally, we comparatively analyzed the similar regulated genes and their involved immune functional processes between DT40 cell and mouse immature B cell line WEHI231 cell with BHP treatment. Results: Following the proposed framework, we proved that the BHP enhanced the mRNA expression levels of IgM in DT40 cells, and induced 460 upregulated genes and 460 downregulated genes in BHP-treated DT40 cells. The pathway analysis showed that the differentially regulated genes in DT40 cell line with BHP treatment were involved in 12 enrichment pathways, in which Toll-like receptor signaling pathway was the vital pathways, and cytokine-cytokine receptor interaction and Jak-STAT signaling pathway were another two important pathways in BHP-treated DT40 cells. Moreover, BHP induced the immune related biological processes in BHP-treated DT40 cells, including T cell related, cytokine related, lymphocyte related, and innate immune response GO terms. Finally, the comparatively analysis showed that there were two downregulated genes GATA3 and IFNG to be found co-existed among the differentially expressed genes in BHP-treated DT40 cell and WEHI231 cells, which shared some same immune related functional processes in both cell lines. Conclusion: After the applying the framework, we proved the inducing roles and the gene expression profiles of BHP on avian immature B cells, and verified some molecular basis from the KEGG and GO analysis. These results provided the insight for mechanism on immature B cell differentiation, and offer the essential direction for the vaccine improvement.



Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 932-932
Author(s):  
Jeff X. Zhou ◽  
Chang-Hoon Lee ◽  
Chen-Feng Qi ◽  
Zohreh Maghashfar ◽  
Ming Zhao ◽  
...  

Abstract The transcription factor, interferon regulatory factor 8 (IRF8), is expressed at low levels in both naïve and terminally differentiated B cells but at high levels in germinal center (GC) B cells where it contributes to transcriptional activation of two genes critically involved in the GC reaction: BCL6, a BTB/POZ-zinc finger transcriptional repressor; and AICDA (also known as AID) a single stranded DNA deaminase (Lee et al. J. Exp. Med.201(1):63–72, 2006). AID is responsible for the generation of double stranded DNA breaks (DSDB) that occur physiologically in B cells during the processes of somatic hypermutation (SHM) of immunoglobulin (Ig) gene variable region sequences and Ig class switch recombination (CSR). The response of most cell types to DSDB is marked by activation of p53 (also termed TP53) that induces cell cycle arrest or apoptosis. p53 also functions at a critical checkpoint to prevent aberrant repair of DSDB in Ig genes that can result in chromosomal translocations that activate proto-oncogenes. GC B cells, however, must be able to tolerate these breaks without experiencing p53-dependent apoptosis. Recent studies showed that functional inactivation of p53 in GC cells is governed in part by transcriptional repression of the p53 gene by BCL6 (Phan and Dalla-Favera Nature432(7017):635–639, 2004). Here we report that IRF8 also suppresses p53 function via transcriptional activation of MDM2. MDM2 is a p53-binding protein and E3 ubiquitin ligase that blocks the transcriptional activity of p53 and stimulates p53 degradation. The levels of both Mdm2 mRNA and its encoded protein were decreased in GC B cells of Irf8 knockout mice as well as in a B lymphoma cell line with siRNA-induced knockdowns of IRF8 expression. Conversely, MDM2 protein levels were increased in cells induced to overexpress IRF8. Transfection of a B lymphoma cell line with an IRF8 expression vector resulted in marked activation of a Mdm2 promoter reporter construct. Oligonucleotide pull-down assays using sequences from the Mdm2 promoter similar to the interferon stimulated response element, a known IRF8 target sequence, were found to bring down IRF8. IL-21, produced by GC T helper cells, promotes the differentiation of B cells activated through the BCR, while inducing apoptosis of unengaged cells. Studies of a B lymphoma cell line treated with IL21 showed that the rate of apoptosis was significantly increased when IRF8 expression was suppressed by siRNAs. The same pattern was true for cells treated with etoposide, a drug that induces DSDB. These results indicate that IRF8 shepherds B cells through the GC reaction by stimulating expression of BCL6 and MDM2 thereby suppressing p53-mediated cell cycle arrest or death in response to DNA breaks.



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