NFκB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation

Rakhesh Madhusoodhanan, Mohan Natarajan, Jamunarani Veeraraghavan, Terence S. Herman, Natarajan Aravindan

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)765-773
Number of pages9
JournalCancer Biology and Therapy
Volume8
Issue number9
DOIs
StatePublished - May 1 2009

Keywords

  • Fractionated irradiation
  • MCF-7
  • NFκB DNA binding activity
  • Radiation induced molecular signaling
  • Radio-adaptive response
  • Transcriptional responses after FIR

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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