scholarly journals Functional Analysis of Promoter Variants in Genes Involved in Sex Steroid Action, DNA Repair and Cell Cycle Control

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 186 ◽  
Author(s):  
Yosr Hamdi ◽  
Martin Leclerc ◽  
Martine Dumont ◽  
Stéphane Dubois ◽  
Martine Tranchant ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Dna Repair ◽  
Cell Cycle Control ◽  
Sex Steroid ◽  
Breast Cancer Cell Lines ◽  
Genome Wide Association Studies ◽  
Promoter Regions ◽  
Functional Variants ◽  
Reporter Assays

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.

Polymorphisms in XRCC1, XRCC3, and CCND1 and Survival After Treatment for Metastatic Breast Cancer

2006 ◽  
Vol 24 (36) ◽  
pp. 5645-5651 ◽  
Author(s):  
Mary A. Bewick ◽  
Michael S.C. Conlon ◽  
Robert M. Lafrenie
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Dna Repair ◽  
Metastatic Breast Cancer ◽  
Bone Metastases ◽  
Cell Cycle Control ◽  
Multivariable Analysis ◽  
Metastatic Breast ◽  
High Dose ◽  
Cancer Specific Survival

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.

983: Bladder Cancer Predisposition: A Pathway-Based Approach to DNA Repair and Cell Cycle Control Genes

2006 ◽  
Vol 175 (4S) ◽  
pp. 317-317
Author(s):  
Xifeng Wu ◽  
Jian Gu ◽  
H. Barton Grossman ◽  
Christopher I. Amos ◽  
Carol Etzel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Dna Repair ◽  
Cell Cycle Control ◽  
Cancer Predisposition

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 ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Gene Targeting ◽  
Cell Cycle Control ◽  
Expression Patterns ◽  
Small Fragment

scholarly journals A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition

2008 ◽  
Vol 415 (1) ◽  
pp. 97-110 ◽  
Author(s):  
Neil E. Torbett ◽  
Antonio Luna-Moran ◽  
Zachary A. Knight ◽  
Andrew Houk ◽  
Mark Moasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Therapeutics ◽  
Cancer Cell Lines ◽  
Genetic Alterations ◽  
Breast Cancer Cell Lines ◽  
Selective Inhibitors

The PI3K (phosphoinositide 3-kinase) pathway regulates cell proliferation, survival and migration and is consequently of great interest for targeted cancer therapy. Using a panel of small-molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we have demonstrated that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110α inhibitors were generally effective in inhibiting the phosphorylation of PKB (protein kinase B)/Akt and S6, two downstream components of PI3K signalling, in most cell lines examined. In contrast, p110β-selective inhibitors only reduced PKB/Akt phosphorylation in PTEN (phosphatase and tensin homologue deleted on chromosome 10) mutant cell lines, and was associated with a lesser decrease in S6 phosphorylation. PI3K inhibitors reduced cell viability by causing cell-cycle arrest in the G1 phase, with multi-targeted inhibitors causing the most potent effects. Cells expressing mutant Ras were resistant to the cell-cycle effects of PI3K inhibition, which could be reversed using inhibitors of Ras signalling pathways. Taken together, our data indicate that these compounds, alone or in suitable combinations, may be useful as breast cancer therapeutics, when used in appropriate genetic contexts.

scholarly journals Paclitaxel and trastuzumab treatment affects insulin growth factor I expression in breast cancer cell lines

2015 ◽  
Vol 10 (4) ◽  
pp. 799 ◽  
Author(s):  
Yu-Xian Qian ◽  
Rui Yu ◽  
Shi-Rong Qin
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Factor I ◽  
Trastuzumab Treatment ◽  
Cycle Arrest

<p class="Abstract">Breast cancer is the most common type of cancers and second primary cause of death among women. Insulin-like growth factor I (IGF-1) signaling pathway plays a vital role in cancer cell survival, proliferation, chemotaxis and angiogenesis. In this study, the effect of combination of two drugs, paclitaxel and trastuzumab on IGF signaling and cell cycle arrest in breast cancer cell lines, T47D and Hs0578T were explored. The interaction of paclitaxel and trastuzumab on IGF-1 signaling pathway was studied with IGF-1 and phosphoinositide 3-kinase inhibitor, LY294002. The protein expression of IGF signaling molecules were reduced in the drug treated cancer cells. LY294002 and IGF-1 with paclitaxel and trastuzumab treatment inhibited phosphorylated Akt. During G0/G1 phase, cell cycle arrest and accumulation of apoptotic cells were observed in drug treated cancer cells. The synergistic effect of paclitaxel and trastuzumab decreased the multiplication of breast cancer cells by altering the expression of IGF-I signaling molecules. This combination proves to be one of the useful methods to treat breast cancer.</p><p> </p>

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