Journal article
Intrinsic radiation resistance in human chondrosarcoma cells
Biochemical and biophysical research communications, Vol.346(2), pp.379-385
2006
DOI: 10.1016/j.bbrc.2006.05.158
PMID: 16765318
Abstract
Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16
ink4a, one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16
ink4a contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16
ink4a expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16
ink4a expression on chondrosarcoma cell resistance to low-dose γ-irradiation (1–5
Gy). p16
ink4a expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16
ink4a transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16
ink4a plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas.
Details
- Title: Subtitle
- Intrinsic radiation resistance in human chondrosarcoma cells
- Creators
- Farid Moussavi-Harami - Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USAAnthony Mollano - Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USAJames A Martin - Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USAAndrew Ayoob - Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USAFrederick E Domann - Department of Radiation Oncology, Iowa City, IA 52245, USASteven Gitelis - Department of Internal Medicine, Section of Medical Oncology, Chicago, IL 60612, USAJoseph A Buckwalter - Departments of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Biochemical and biophysical research communications, Vol.346(2), pp.379-385
- DOI
- 10.1016/j.bbrc.2006.05.158
- PMID
- 16765318
- NLM abbreviation
- Biochem Biophys Res Commun
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2006
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Surgery; Radiation Oncology; Injury Prevention Research Center
- Record Identifier
- 9984040003702771
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