NF-B

Friend? (or) Foe?

in

CANCER
 INTRODUCTION

“Man proposes God disposes”

Things One edge Other edge

TNF Strengthens immune system inflammation and cancer
c-myc apoptosis cell proliferation

AP-1 apoptosis cell proliferation

 What is NF-B?
 Nuclear transcription factor.

 Discovered by Sen & Baltimore in 1986.

 In the kappa chain of Ig in B cells.

 Stimulates the expression of over 200 genes.

 Control the immune system, growth and inflammation.

 NF-B Family
 NF-kB1(p105&p50)

 NF-Kb(p100&p52)

 Rel A(p65)

 Rel B

 c Rel

 All vertebral cells express atleast one of five Rel/NF-B

Members.

 Assembled into homo or hetero dimers.

NF-B Activation.
NF-B Inhibition.
NF-B AS A FRIEND

 Regulate immune function.

 Enhance apoptosis
 Maintains haematopoiesis.
 Prevents tumourogenesis
 NF-B and immune system
MICROBES

NF-B activation

Induction of genes encoding cytokines chemokines enzymes and

antimicrobial peptides.

Build the first line defense against bacteria and fungi

NF-B mediates apoptosis
Oxidative stress
TNF Fas

NF-B ACTIVATION

• Down regulation of bcl2

• Translocation of bax
• Upregulation of p53

APOPTOSIS
NF-B prevents tumourogenesis
NF-B inhibition in epidermis

Increased production of TNF

Responsible for inflammatory response

Keratinocyte hyperproliferation

Development of squamous cell carcinoma

 NF-B and Haematopoiesis
Defect in lymphopoiesis
P65(-/-) Fetal liver cells
Normal development of
Myeloid & granulocyte
Lineage.
Arrest B cell
P50&p52 Development
Affects progenitor
Maturation
Reduced CFU progenitors
Impaired erythropoiesis
P65&c Rel
Aberrant expansion of
Granulocyte & macrophage
apoptosis
NF-B AS A FOE

 Enhance tumourogenesis
 Suppress apoptosis
 Links inflammation to cancer

 Develop chemoresistance
NF-B PROMOTES TUMOUROGENESIS
NF-B suppress Apoptosis

Inflammatory stimuli (TNF 

NF-B activation

Antiapoptotic proteins

Cell proliferation and inhibition of apoptosis

NF-B Links Inflammation and Cancer
NF-B develops chemoresistance
NF-B: FRIEND? OR FOE?
 CONCLUSION
 Clinical observations implicate
1. NF-B activation prevents skin cancer
2. NF-B activation promotes various cancers
 Challenges
• To figure out the molecular mechanisms that dictate the
pro-oncogenic or anti-oncogenic activity of NF-B.
• To find out compounds which blocks the oncogenic
activity of NF-B without interfering the normal
physiological roles.