Constitutive activation of nuclear factor-kappaB is preferentially involved in the proliferation of basal-like subtype breast cancer cell lines.
Constitutive nuclear factor (NF)-kappaB activation is thought to be involved in survival, invasion, and metastasis in various types of cancers. However, neither the subtypes of breast cancer cells with constitutive NF-kappaB activation nor the molecular mechanisms leading to its constitutive activation have been clearly defined. Here, we quantitatively analyzed basal NF-kappaB activity in 35 human breast cancer cell lines and found that most of the cell lines with high constitutive NF-kappaB activation were categorized in the estrogen receptor negative, progesterone receptor negative, ERBB2 negative basal-like subtype, which is the most malignant form of breast cancer. Inhibition of constitutive NF-kappaB activation by expression of IkappaBalpha super-repressor reduced proliferation of the basal-like subtype cell lines. Expression levels of mRNA encoding NF-kappaB-inducing kinase (NIK) were elevated in several breast cancer cell lines, and RNA interference-mediated knockdown of NIK reduced NF-kappaB activation in a subset of the basal-like subtype cell lines with upregulated NIK expression. Taken together, these results suggest that constitutive NF-kappaB activation, partially dependent on NIK, is preferentially involved in proliferation of basal-like subtype breast cancer cells and may be a useful therapeutic target for this subtype of cancer.
Yamaguchi
Noritaka
N
Department of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo.
Ito
Taku
T
Azuma
Sakura
S
Ito
Emi
E
Honma
Reiko
R
Yanagisawa
Yuka
Y
Nishikawa
Akira
A
Kawamura
Mika
M
Imai
Jun-ichi
J
Watanabe
Shinya
S
Semba
Kentaro
K
Inoue
Jun-ichiro
J
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097782:NF-kappaB-Inducing Kinase
D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000097782:NF-kappaB-Inducing Kinase; C508053:ERBB2 protein, human