scholarly journals The Gene Targeting Approach of Small Fragment Homologous Replacement (SFHR) Alters the Expression Patterns of DNA Repair and Cell Cycle Control Genes

2016 ◽  
Vol 5 ◽  
pp. e304 ◽  
Author(s):  
Silvia Pierandrei ◽  
Andrea Luchetti ◽  
Massimo Sanchez ◽  
Giuseppe Novelli ◽  
Federica Sangiuolo ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Sarayut Radapong ◽  
Kelvin Chan ◽  
Satyajit D. Sarker ◽  
Kenneth J. Ritchie

Oxyresveratrol (OXY) is a small molecule of phytochemical known as hydroxystilbenoids, which have been reported significantly important biological activities. The aim of this study was to elucidate the gene expression and biological pathways altered in MCF7, breast cancer cells. The cytotoxicity to different cancer cell lines was screened using MTT assay and then whole gene expression was elucidated using microarray. The pathways selected also validated by quantitative PCR analysis, fluorometric and western blot assay. A total of 686 genes were found to have altered mRNA expression levels of two-fold or more in the 50 μM OXY-treated group, while 2,338 genes were differentially expressed in the 100 µM-treated group. The relevant visualized global expression patterns of genes and pathways were generated. Apoptosis was activated through mitochondria-lost membrane potential, caspase-3 expression and chromatin condensation without DNA damage. G0/G1 and S phases of the cell cycle control were inhibited dose-dependently by the compound. Rad51 gene (DNA repair pathway) was significantly down-regulated (p < 0.0001). These results indicated that OXY moderated the key genes and pathways in MCF7 cells that could be developed as chemotherapy or chemo-sensitizing agent.


2006 ◽  
Vol 175 (4S) ◽  
pp. 317-317
Author(s):  
Xifeng Wu ◽  
Jian Gu ◽  
H. Barton Grossman ◽  
Christopher I. Amos ◽  
Carol Etzel ◽  
...  

2010 ◽  
Vol 118 (2) ◽  
pp. 404-410 ◽  
Author(s):  
Aijuan Qu ◽  
Yatrik M. Shah ◽  
Tsutomu Matsubara ◽  
Qian Yang ◽  
Frank J. Gonzalez

2006 ◽  
Vol 24 (36) ◽  
pp. 5645-5651 ◽  
Author(s):  
Mary A. Bewick ◽  
Michael S.C. Conlon ◽  
Robert M. Lafrenie

Purpose Single nucleotide polymorphisms (SNPs) in DNA repair and cell cycle control genes may alter protein function and therefore the efficacy of DNA damaging chemotherapy. We retrospectively evaluated the association of SNPs in DNA repair genes, XRCC1-01 (Arg399Gln) and XRCC3-01 (Thr241Met), and a cell cycle control gene, CCND1-02 (A870G), with progression-free survival (PFS) and breast cancer specific survival (BCSS) in patients with metastatic breast cancer (MBC). Patients and Methods SNPs in 95 patients with MBC enrolled onto one of five prospective clinical trials of high-dose chemotherapy and autologous stem-cell transplantation were evaluated using genotyping assays. Results For XRCC1-01, the hazard ratio (HR) for BCSS was 2.8 (95% CI, 1.60 to 5.00) and the HR for PFS was 2.0 (95%CI, 1.12 to 3.43). For XRCC3-01, the HR for BCSS was 2.0 (95%CI, 1.12 to 3.70) and the HR for PFS was 2.0 (95%CI, 1.09 to 3.59). For CCND1-02, the HR for BCSS was 1.8 (95%CI, 1.12 to 2.78) and the HR for PFS was 1.8 (95%CI, 1.15 to 2.85). Patients carrying one variant genotype (HR, 1.7; 95%CI, 1.07 to 2.82) or combinations of any two variant genotypes (HR, 4.7; 95% CI, 2.41 to 8.94) had significantly poorer BCSS compared with patients carrying zero variants. In multivariable analysis, XRCC1-01, presence of liver metastases, and bone metastases independently predicted BCSS. Combinations of any two variant genotypes were stronger independent predictors of BCSS and PFS than the presence of liver or bone metastases. Conclusion XRCC1-01, XRCC3-01, and CCND1-01 may be predictive of survival outcome in patients with MBC treated with DNA damaging chemotherapy.


2006 ◽  
Vol 78 (3) ◽  
pp. 464-479 ◽  
Author(s):  
Xifeng Wu ◽  
Jian Gu ◽  
H. Barton Grossman ◽  
Christopher I. Amos ◽  
Carol Etzel ◽  
...  

2002 ◽  
Vol 10 (2) ◽  
pp. 103-111 ◽  
Author(s):  
Jennifer L. Moran ◽  
Yizheng Li ◽  
Andrew A. Hill ◽  
William M. Mounts ◽  
Christopher P. Miller

Studies described here utilize high-density oligonucleotide arrays to characterize changes in global mRNA expression patterns during proliferation, cell cycle withdrawal, and terminal differentiation in mouse C2C12 myoblasts. Statistical analyses revealed 629 sequences differentially regulated between proliferating and differentiating myoblasts. These genes were clustered using self-organizing maps to identify sets of coregulated genes and were assigned to functional categories that were analyzed for distribution across expression clusters. Clusters were identified with statistically significant enrichment of functional categories including muscle contraction, cell adhesion, extracellular matrix function, cellular metabolism, mitochondrial transport, DNA replication, cell cycle control, mRNA transcription, and unexpectedly, immune regulation. In addition, functional category enrichment data can be used to predict gene function for numerous differentially regulated expressed sequence tags. The results provide new insight into how genes involved in these cellular processes may play a role in skeletal muscle growth and differentiation.


2021 ◽  
Vol 32 (4) ◽  
pp. 74-82
Author(s):  
Yailit del Carmen Martinez-Vargas ◽  
Tiago João da Silva-Filho ◽  
Denise Hélen Imaculada Pereira de Oliveira ◽  
Rani Iani Costa Gonçalo ◽  
Lélia Maria Guedes Queiroz

Abstract The Inhibitor of Growth (ING) gene family is a group of tumor suppressor genes that play important roles in cell cycle control, senescence, DNA repair, cell proliferation, and apoptosis. However, inactivation and downregulation of these proteins have been related in some neoplasms. The present study aimed to evaluate the immunohistochemical profiles of ING3 and ING4 proteins in a series of benign epithelial odontogenic lesions. Methods: The sample comprised of 20 odontogenic keratocysts (OKC), 20 ameloblastomas (AM), and 15 adenomatoid odontogenic tumors (AOT) specimens. Nuclear and cytoplasmic immunolabeling of ING3 and ING4 were semi-quantitatively evaluated in epithelial cells of the odontogenic lesions, according to the percentage of immunolabelled cells in each case. Descriptive and statistics analysis were computed, and the p-value was set at 0.05. Results: No statistically significant differences were found in cytoplasmic and nuclear ING3 immunolabeling among the studied lesions. In contrast, AOTs presented higher cytoplasmic and nuclear ING4 labeling compared to AMs (cytoplasmic p-value = 0.01; nuclear p-value < 0.001) and OKCs (nuclear p-value = 0.007). Conclusion: ING3 and ING4 protein downregulation may play an important role in the initiation and progression of more aggressive odontogenic lesions, such as AMs and OKCs.


Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 186 ◽  
Author(s):  
Yosr Hamdi ◽  
Martin Leclerc ◽  
Martine Dumont ◽  
Stéphane Dubois ◽  
Martine Tranchant ◽  
...  

Genetic variants affecting the regulation of gene expression are among the main causes of human diversity. The potential importance of regulatory polymorphisms is underscored by results from Genome Wide Association Studies, which have already implicated such polymorphisms in the susceptibility to complex diseases such as breast cancer. In this study, we re-sequenced the promoter regions of 24 genes involved in pathways related to breast cancer including sex steroid action, DNA repair, and cell cycle control in 60 unrelated Caucasian individuals. We constructed haplotypes and assessed the functional impact of promoter variants using gene reporter assays and electrophoretic mobility shift assays. We identified putative functional variants within the promoter regions of estrogen receptor 1 (ESR1), ESR2, forkhead box A1 (FOXA1), ubiquitin interaction motif containing 1 (UIMC1) and cell division cycle 7 (CDC7). The functional polymorphism on CDC7, rs13447455, influences CDC7 transcriptional activity in an allele-specific manner and alters DNA–protein complex formation in breast cancer cell lines. Moreover, results from the Breast Cancer Association Consortium show a marginal association between rs13447455 and breast cancer risk (p=9.3x10-5), thus warranting further investigation. Furthermore, our study has helped provide methodological solutions to some technical difficulties that were encountered with gene reporter assays, particularly regarding inter-clone variability and statistical consistency.


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