Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 6, Pages 1714-1719Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0308102100
Keywords
IFN signaling; acquired tumor radioresistance; microarrays; HSV-1 replication in tumors
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Funding
- NCI NIH HHS [P01 CA071933, CA 71933, CA 78766, R37 CA078766, R01 CA078766] Funding Source: Medline
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Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Replicate DNA array experiments identified 52 genes differentially expressed in nu61 tumors compared with SCC-61 tumors. Of these, 19 genes were in the IFN-signaling pathway and moreover, 25 of the 52 genes were inducible by IFN in the nu61 cell line. Among the genes involved in IFN signaling, STAT1alpha and STAT1beta were the most highly over expressed in nu61 compared to SCC-61. STAT1alpha and STAT1beta cDNAs were cloned and stably transfected into SCC-61 tumor cells. Clones of SCC-61 tumor cells transfected with vectors expressing STAT1alpha and STAT1beta demonstrated radioprotection after exposure to 3 Gy (P < 0.038). The results indicate that radioresistance acquired during radiotherapy treatment may account for some treatment failures and demonstrate an association of acquired tumor radioresistance with up-regulation of components of the IFN-related signaling pathway.
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