Journal of Mammary Gland Biology and Neoplasia

, Volume 11, Issue 1, pp 63–73

Exploiting Our Knowledge of NF-κB Signaling for the Treatment of Mammary Cancer

  • Michael C. Haffner
  • Chiara Berlato
  • Wolfgang Doppler
Article

DOI: 10.1007/s10911-006-9013-5

Cite this article as:
Haffner, M.C., Berlato, C. & Doppler, W. J Mammary Gland Biol Neoplasia (2006) 11: 63. doi:10.1007/s10911-006-9013-5

Abstract

Nuclear Factor-kappaB (NF-κB) has been implicated in the lobuloalveolar development of the mammary gland. In breast cancer its activation has been linked to tumor progression via stimulation of cell proliferation, pro-survival, and angiogenesis pathways and metastasis. Whether NF-κB activation in the immune system influences mammary cancer remains unclear. In addition to the constitutive activation frequently found in mammary carcinoma tissue, radio- and chemotherapeutic agents used in the treatment of mammary cancer can lead to activation of NF-κB. This effect has been postulated to contribute to the development of resistance to these agents and suggests the use of NF-κB inhibitors as sensitizers for therapy. The review describes principle targets and drugs used to inhibit NF-κB function and discusses future perspectives in the use of these inhibitors for the treatment of mammary cancer.

Keywords

NF-κB Breast cancer Proteasome Apoptosis Metastasis Chemosensitization 

Abbreviations

AP-1

activator protein 1

CAT

chlor-amphenicol-acetyltransferase

CHIP

chromatin immunoprecipitation

CK2

casein kinase 2

COX

cyclooxygenase

DHMEQ

dehydroxymethylepoxyquinomicin

DMBA

7,12-dimethylbenz[a]anthracene

3-Cl-AHPC

4-[3-Cl-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid

ELISA

enzyme-linked immunosorbent assay

EMSA

electrophoretic mobility shift assay

ER

estrogen receptor

GSK3

glycogen synthase kinase 3

ICAM

intercellular adhesion molecule

IGF

insulin-like growth factor

IGF-IR

insulin-like growth factors I receptor

IκB

inhibitor of kappaB

IKK

IkappaB kinase

IL

interleukin

MEF

mouse embryonic fibroblast

MMP

matrix metalloproteinase

NEMO

NF-κB essential modulator

NF-κB

Nuclear Factor-kappaB

NIK

NF-kappaB-inducing kinase

NK cells

natural killer cells

NLS

nuclear localization sequence

NSAID

non-steroidal anti-inflammatory drugs

PI3-kinase

Phosphatidylinositol-3-kinase

RANK

receptor activator of NF-κB

RANKL

receptor activator of NF-κB ligand

RHD

Rel homology domain

RT-PCR

reverse-transcription-polymerase chain reaction

SCID

severe combined immunodeficiency

STAT

signal transducer and activator of transcription

TAM

tumor-associated macrophage

TGF

transforming growth factor

TNF

tumor necrosis factor

VCAM

vascular cell adhesion molecule

VEGF

vascular endothelial growth factor

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Michael C. Haffner
    • 1
  • Chiara Berlato
    • 1
  • Wolfgang Doppler
    • 1
  1. 1.Division Medical Biochemistry, BiocenterInnsbruck Medical UniversityInnsbruckAustria

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