TY - JOUR
T1 - NFκB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation
AU - Madhusoodhanan, Rakhesh
AU - Natarajan, Mohan
AU - Veeraraghavan, Jamunarani
AU - Herman, Terence S
AU - Aravindan, Natarajan
N1 - Funding Information:
This work was supported by Department of Radiation Oncology research development funds and American Cancer Society institutional review grant (ACS-IRG-05-066-01) to Natarajan Aravindan.
PY - 2009/5/1
Y1 - 2009/5/1
N2 - Radiotherapy is considered mandatory for breast cancer patients undergoing conservative surgery and for women at high risk of recurrence. However, relapse due to radio-resistance affects the success of radiotherapy. Ascertaining the fractionated radiation (FIR) modulated molecular targets is important to make tumors more susceptible to molecular targeted therapy. Accordingly, we investigated the (i) expression of 84 genes representing six functional pathways; (ii) NFκB DNA binding activity and; (iii) expression of radio-responsive molecules after single dose (10Gy) radiation (SDR) and FIR (2Gyx5). MCF-7 cells exposed to SDR or FIR were analyzed for alterations in gene expression using QPCR-profiling. NFκB DNA binding activity was analyzed using EMSA and pIκB using immunoblotting. Expression of TNFα, IL-1α, pAKT, IAP1, IAP2, XIAP, survivin, MnSOD, BID and Bak were determined using QPCR and/or immunoblotting. Compared to SDR, FIR significantly induced 60 genes and completely suppressed 14 genes. Furthermore, FIR induced NFκB-DNA binding activity and IκBα phosphorylation. Like-wise, FIR induced the expression of IAP1, IAP2, XIAP Survivin, MnSOD, TNFα, pAKT and IL-1α. The results of the study clearly show distinct differences in the molecular response of cells between SDR and FIR exposures. We identified several potential targets that may affect radio-resistance following FIR.
AB - Radiotherapy is considered mandatory for breast cancer patients undergoing conservative surgery and for women at high risk of recurrence. However, relapse due to radio-resistance affects the success of radiotherapy. Ascertaining the fractionated radiation (FIR) modulated molecular targets is important to make tumors more susceptible to molecular targeted therapy. Accordingly, we investigated the (i) expression of 84 genes representing six functional pathways; (ii) NFκB DNA binding activity and; (iii) expression of radio-responsive molecules after single dose (10Gy) radiation (SDR) and FIR (2Gyx5). MCF-7 cells exposed to SDR or FIR were analyzed for alterations in gene expression using QPCR-profiling. NFκB DNA binding activity was analyzed using EMSA and pIκB using immunoblotting. Expression of TNFα, IL-1α, pAKT, IAP1, IAP2, XIAP, survivin, MnSOD, BID and Bak were determined using QPCR and/or immunoblotting. Compared to SDR, FIR significantly induced 60 genes and completely suppressed 14 genes. Furthermore, FIR induced NFκB-DNA binding activity and IκBα phosphorylation. Like-wise, FIR induced the expression of IAP1, IAP2, XIAP Survivin, MnSOD, TNFα, pAKT and IL-1α. The results of the study clearly show distinct differences in the molecular response of cells between SDR and FIR exposures. We identified several potential targets that may affect radio-resistance following FIR.
KW - Fractionated irradiation
KW - MCF-7
KW - NFκB DNA binding activity
KW - Radiation induced molecular signaling
KW - Radio-adaptive response
KW - Transcriptional responses after FIR
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U2 - 10.4161/cbt.8.9.8105
DO - 10.4161/cbt.8.9.8105
M3 - Article
C2 - 19276662
AN - SCOPUS:68149164689
SN - 1538-4047
VL - 8
SP - 765
EP - 773
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 9
ER -