Journal article
Impaired homologous recombination DNA repair and enhanced sensitivity to DNA damage in prostate cancer cells exposed to anchorage-independence
Oncogene, v 24(23), pp 3748-3758
26 May 2005
PMID: 15782124
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
During metastases, cancer cells are temporarily exposed to the condition in which interactions with extracellular environment can be restricted (anchorage-independence). We demonstrate that the sensitivity of prostate cancer cell lines, DU145 and PC-3, to genotoxic treatment (cisplatin and gamma-irradiation) increased several folds when cells were forced to grow in anchorage-independence. This enhanced drug sensitivity was associated with a severe impairment of homologous recombination-directed DNA repair (HRR). The mechanism involves Rad51, which is the major enzymatic component of HRR. The protein level of Rad51 and its recruitment to DNA double-strand breaks (DSBs) were both attenuated. Rad51 deficiency in anchorage-independence was not associated with Rad51 promoter activity, and was not compensated by a constitutive overexpression of Rad51 cDNA. Instead, Rad51 protein level and its ability to colocalize with DSBs were restored in the presence of proteosome inhibitors, or when cells from the suspension cultures were allowed reattachment. Presented results indicate that anchorage-independence sensitizes prostate cancer cells to genotoxic agents; however, it also attenuates faithful component of DNA repair by targeting stability of Rad51. This temporal attenuation of HRR may contribute to the accumulation mutations after DNA damage, and possibly the selection of new adaptations in cells, which survived genotoxic treatment.
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Details
- Title
- Impaired homologous recombination DNA repair and enhanced sensitivity to DNA damage in prostate cancer cells exposed to anchorage-independence
- Creators
- Jin Ying Wang - Temple UniversityThu Ho - Temple UniversityJoanna Trojanek - Temple UniversityJanaki Chintapalli - Temple UniversityMaja Grabacka - Temple UniversityTomasz Stoklosa - Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, USAFernando U Garcia - Drexel UniversityTomasz Skorski - Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, USAKrzysztof Reiss - Temple University
- Publication Details
- Oncogene, v 24(23), pp 3748-3758
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pathology (and Laboratory Medicine)
- Web of Science ID
- WOS:000229346300006
- Scopus ID
- 2-s2.0-19844376479
- Other Identifier
- 991019168146904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Genetics & Heredity
- Oncology