Identification of proteins that regulate radiation-induced apoptosis in murine tumors with wild type p53

In this study, we investigated the molecular factors determining the induction of apoptosis by radiation. Two murine tumors syngeneic to C3H/HeJ mice were used: an ovarian carcinoma OCa-I, and a hepatocarcinoma HCa-I. Both have wild type p53, but display distinctly different radiosensitivity in term...

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Bibliographic Details
Published in:Journal of radiation research 2007-09, Vol.48 (5), p.435-441
Main Authors: Seong, Jinsil, Oh, Hae Jin, Kim, Jiyoung, An, Jeung Hee, Kim, Wonwoo
Format: Article
Language:English
Subjects:
Animals
Apoptosis - radiation effects
Apoptosis Regulatory Proteins - metabolism
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Dose-Response Relationship, Radiation
Female
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Mice
Mice, Inbred C3H
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Radiation Dosage
Tumor Suppressor Protein p53 - metabolism
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Summary:In this study, we investigated the molecular factors determining the induction of apoptosis by radiation. Two murine tumors syngeneic to C3H/HeJ mice were used: an ovarian carcinoma OCa-I, and a hepatocarcinoma HCa-I. Both have wild type p53, but display distinctly different radiosensitivity in terms of specific growth delay (12.7 d in OCa-I and 0.3 d in HCa-I) and tumor cure dose 50% (52.6 Gy in OCa-I and > 80 Gy in HCa-I). Eight-mm tumors on the thighs of mice were irradiated with 25 Gy and tumor samples were collected at regular time intervals after irradiation. The peak levels of apoptosis were 16.1 +/- 0.6% in OCa-I and 0.2 +/- 0.0% in HCa-I at 4 h after radiation, and this time point was used for subsequent proteomics analysis. Protein spots were identified by peptide mass fingerprinting with a focus on those related to apoptosis. In OCa-I tumors, radiation increased the expression of cytochrome c oxidase and Bcl2/adenovirus E1B-interacting 2 (Nip 2) protein higher than 3-fold. However in HCa-I, these two proteins showed no significant change. The results suggest that radiosensitivity in tumors with wild type p53 is regulated by a complex mechanism. Furthermore, these proteins could be molecular targets for a novel therapeutic strategy involving the regulation of radiosensitivity.
ISSN:0449-3060
1349-9157
DOI:10.1269/jrr.07015