TY - JOUR
T1 - Mechanisms of X-ray-mediated protooncogene c-iun expression in radiation-induced human sarcoma cell lines
AU - Hallahan, Dennis E.
AU - Virudachalam, Subbulakshmi
AU - Beckett, Michael
AU - Sherman, Matthew L.
AU - Kufe, Donald
AU - Weichselbaumi, Ralph R.
N1 - Funding Information:
The methods for the establishment of cell lines was previously described (26). Briefly, tumor explants were diced mor samples and M. Karin for the c-jun plasmid. Funding for this research includes: The Pasis Fund, Chicago Tumor Institute, Center for Radiation Therapy, and NC1 Grant CA 41068. Accepted for publication 12 September 1991.
PY - 1991/11
Y1 - 1991/11
N2 - 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.
AB - 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.
KW - Radiation-induced human sarcomas
KW - X-ray-mediated gene expression
KW - c-jun protooncogene
UR - http://www.scopus.com/inward/record.url?scp=0025919744&partnerID=8YFLogxK
U2 - 10.1016/0360-3016(91)90352-5
DO - 10.1016/0360-3016(91)90352-5
M3 - Article
C2 - 1801783
AN - SCOPUS:0025919744
SN - 0360-3016
VL - 21
SP - 1677
EP - 1681
JO - International journal of radiation oncology, biology, physics
JF - International journal of radiation oncology, biology, physics
IS - 6
ER -