Mechanisms of X-ray-mediated protooncogene c-iun expression in radiation-induced human sarcoma cell lines

Dennis E. Hallahan, Subbulakshmi Virudachalam, Michael Beckett, Matthew L. Sherman, Donald Kufe, Ralph R. Weichselbaumi

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

c-jun is a protooncogene associated with neoplastic transformation and is transcriptionally induced by ionizing radiation. To examine the possible mechanisms of radiation-induced c-jun transcription, we analyzed RNA from human tumor cell lines RIT-3 and STSAR-5 following x-irradiation in the presence of protein kinase inhibitors, or the absence of serum and calcium. Protoonocogene c-jun expression increased several fold following irradiation of these radiation-induced human sarcoma cell lines. The expression of cjun was not altered following irradiation in conditioned medium containing serum as compared to that of cells in serum free medium. Depletion of PKC by prolonged TPA treatment resulted in inhibition of c-jun expression. In addition, nonspecific protein kinase inhibitors, staurosporin and H7 attenuated c-jun expression, whereas the analogue of ATP (sangivamycin) did not. Furthermore, the selective inhibitor of cAMP dependent protein kinase HA 1004 did not alter radiation-mediated c-jun induction. These data indicate that ionizing radiation exposure results in c-jun induction which is dependent upon the activation of PKC. Protein kinase C activation and the subsequent expression of the protooncogene c-jun by ionizing radiation may further define the molecular mechanisms of radiation-induced neoplastic transformation.

Original languageEnglish
Pages (from-to)1677-1681
Number of pages5
JournalInternational journal of radiation oncology, biology, physics
Volume21
Issue number6
DOIs
StatePublished - Nov 1991

Keywords

  • Radiation-induced human sarcomas
  • X-ray-mediated gene expression
  • c-jun protooncogene

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