scholarly journals Identification of DNA Repair Pathways That Affect the Survival of Ovarian Cancer Cells Treated with a Poly(ADP-Ribose) Polymerase Inhibitor in a Novel Drug Combination

2012 ◽  
Vol 82 (4) ◽  
pp. 767-776 ◽  
Author(s):  
Amelia M. Huehls ◽  
Jill M. Wagner ◽  
Catherine J. Huntoon ◽  
Larry M. Karnitz
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Cancer Cells ◽  
Drug Combination ◽  
Ovarian Cancer Cells ◽  
Polymerase Inhibitor ◽  
Repair Pathways ◽  
Novel Drug

scholarly journals Wild-Type Tumor Repressor Protein 53 (TRP53) Promotes Ovarian Cancer Cell Survival

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1638-1648 ◽  
Author(s):  
Lisa K. Mullany ◽  
Zhilin Liu ◽  
Erin R. King ◽  
Kwong-Kwok Wong ◽  
JoAnne S. Richards
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Ovarian Cancer ◽  
Dna Repair ◽  
Cell Survival ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Low Grade ◽  
Wild Type ◽  
Repressor Protein

Loss of Pten in the KrasG12D;Amhr2-Cre mutant mice leads to the transformation of ovarian surface epithelial (OSE) cells and rapid development of low-grade, invasive serous adenocarcinomas. Tumors occur with 100% penetrance and express elevated levels of wild-type tumor repressor protein 53 (TRP53). To test the functions of TRP53 in the Pten;Kras (Trp53+) mice, we disrupted the Trp53 gene yielding Pten;Kras(Trp53−) mice. By comparing morphology and gene expression profiles in the Trp53+ and Trp53− OSE cells from these mice, we document that wild-type TRP53 acts as a major promoter of OSE cell survival and differentiation: cells lacking Trp53 are transformed yet are less adherent, migratory, and invasive and exhibit a gene expression profile more like normal OSE cells. These results provide a new paradigm: wild-type TRP53 does not preferentially induce apoptotic or senescent related genes in the Pten;Kras(Trp53+) cancer cells but rather increases genes regulating DNA repair, cell cycle progression, and proliferation and decreases putative tumor suppressor genes. However, if TRP53 activity is forced higher by exposure to nutlin-3a (a mouse double minute-2 antagonist), TRP53 suppresses DNA repair genes and induces the expression of genes that control cell cycle arrest and apoptosis. Thus, in the Pten;Kras(Trp53+) mutant mouse OSE cells and likely in human TP53+ low-grade ovarian cancer cells, wild-type TRP53 controls global molecular changes that are dependent on its activation status. These results suggest that activation of TP53 may provide a promising new therapy for managing low-grade ovarian cancer and other cancers in humans in which wild-type TP53 is expressed.

scholarly journals Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells

Oncotarget ◽  
2014 ◽  
Vol 5 (9) ◽  
pp. 2678-2687 ◽  
Author(s):  
Young Eun Choi ◽  
Chiara Battelli ◽  
Jacqueline Watson ◽  
Joyce Liu ◽  
Jennifer Curtis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Sublethal Concentrations

scholarly journals ALDH1A1 Contributes to PARP Inhibitor Resistance via Enhancing DNA Repair in BRCA2−/− Ovarian Cancer Cells

2019 ◽  
Vol 19 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Lu Liu ◽  
Shurui Cai ◽  
Chunhua Han ◽  
Ananya Banerjee ◽  
Dayong Wu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Cancer Cells ◽  
Parp Inhibitor ◽  
Ovarian Cancer Cells ◽  
Inhibitor Resistance

Inhibitory Effect of the Zinc Metallochaperone NSC319726 on Ovarian Cancer Cells via the Regulation of P53

2021 ◽  
Author(s):  
Shikui Sun ◽  
Yue Liang ◽  
Ke Li ◽  
Yizhen Wang ◽  
Huimin Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Suppressor Gene ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Cyclin Dependent Kinase ◽  
Tumor Protein P53 ◽  
Novel Drug

Abstract Ovarian cancer is the leading cause of death from malignancies of the female reproductive system. In recent years, there has been little development regarding the treatment of ovarian cancer. Wild-type tumor protein p53 (P53) can inhibit the development of tumor, however, mutations in P53 have been shown in most cases of ovarian cancer. The mutated gene encoded P53 transforms from a tumor suppressor gene to an oncogene, losing its original anti-tumor function. Studies have shown that the zinc metallochaperone NSC319726 can promote the correct folding of P53 in cancer cells and restore its physiological function, however, the function of NSC319726 in ovarian cancer has not been elaborated. So we investigated the role of NSC319726 on biological functions of ovarian cancer and preliminarily determined the specific molecular mechanism. The results showed that NSC319726 could inhibit proliferation, migration and invasion of ovarian cancer cells and promote their apoptosis. Mechanically, NSC319726 regains the tumor-suppressed function of P53, further activates the downstream cyclin-dependent kinase CDK inhibited protein P21, thereby blocking the cell cycle and inhibiting cells proliferation. Therefore, NSC319726 has the potential to act as a novel drug for treating ovarian cancer.

Evaluating the potential of kinase inhibitors to suppress DNA repair and sensitise ovarian cancer cells to PARP inhibitors

2019 ◽  
Vol 167 ◽  
pp. 125-132 ◽  
Author(s):  
Asima Mukhopadhyay ◽  
Yvette Drew ◽  
Elizabeth Matheson ◽  
Mo Salehan ◽  
Lucy Gentles ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Cancer Cells ◽  
Kinase Inhibitors ◽  
Parp Inhibitors ◽  
Ovarian Cancer Cells
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