UNASSIGNED: Understanding the underlying mechanism by which @entity5 cells acquire resistance to radiation and favorably selected for its clonal expansion will provide molecular insight into @entity5 recurrence at the treatment site. In the present study, we investigated the molecular mechanisms prompted in MCF-7 @entity0 cells in response to clinical radiation and the associated coordination of intra- and inter-cellular signaling that orchestrate radio-resistance and @entity5 relapse/recurrence. Our findings showed that 2 or 10Gy of (137)Cs y- @entity16039 at a dose rate of 1.03Gy/min trigger the activation of nuclear factor kappa B (NF-kB), its DNA-binding activity and recycles its own transcription. NF-kB DNA-binding kinetic analysis demonstrated both sustained and dual phase NF-kB activation with radiation. Gene manipulation approach revealed that radiation triggered NF-kB-mediated @entity310 transcriptional activity. @entity310 blocking approach confirmed that the de novo synthesis and secretion of @entity310 serves as a pre-requisite for the second phase of NF-kB activation and sustained maintenance. Radiation-associated NF-kB-dependent secretion of @entity310 from irradiated cells, in parallel, activates NF-kB in the non-targeted un-irradiated bystander cells. Together, these findings demonstrated that radiation-triggered NF-kB-dependent @entity310 secretion is critical for self-sustenance of NF-kB (through autocrine positive feedback signaling) and for coordinating bystander response (through inter-cellular paracrine mechanism) after radiation exposure. Further, the data suggest that this self-sustained NF-kB in the irradiated cells determines radio-resistance, survival advantage and clonal expansion of the @entity5 cells at the treatment site. Parallel maintenance of NF-  B- @entity310 -NF-kB feedback-cycle in the un-irradiated non-targeted bystander cells initiates supportive mechanism for the promotion and progression of surviving @entity5 cells. Intervening this molecular pathway would help us to achieve disease-free @entity5 survivors.

Inter- and intra-cellular mechanism of NF-kB-dependent survival advantage and clonal expansion of radio-resistant XXXX cells.

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity310 :: ('7124', 'Gene') :: ['TNFa', 'TNF-a'] @entity16039 :: ('255564', 'Species') :: ['rays'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer']
@entity5 :: (MESH:D009369,Disease) :: ['cancer']
