Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3

Citation
Pc. Cogswell et al., Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3, ONCOGENE, 19(9), 2000, pp. 1123-1131
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
19
Issue
9
Year of publication
2000
Pages
1123 - 1131
Database
ISI
SICI code
0950-9232(20000224)19:9<1123:SAONBS>2.0.ZU;2-G
Abstract
Members of the NF-kappa B/Rel transcription factor family have been shown r ecently to be required for cellular transformation by oncogenic Ras and by other oncoproteins and to suppress transformation-associated apoptosis. Fur thermore, NF-kappa B has been shown to be activated by several oncoproteins including HER2/Neu, a receptor tyrosine kinase often expressed in human br east cancer. Human breast cancer cell lines, human breast tumors and normal adjacent tissue were analysed by gel mobility shift assay, immunoblotting of nuclear extracts and immunohistochemistry for activation of NF-kappa B, Furthermore, RNA levels for NF-kappa B-activated genes were analysed in ord er to determine if NF-kappa B is functionally active in human breast cancer . Our data indicate that the p65/RelA subunit of NF-kappa B is activated (i .e., nuclear) in breast cancer cell lines. However, breast tumors exhibit a n absence or low level of nuclear p65/RelA but show activated c-Rel, p50 an d p52 as compared to nontumorigenic adjacent tissue. Additionally, the I ka ppa B homolog Bcl-3, which functions to stimulate transcription with p50 or p52, was also activated in breast tumors. There was no apparent correlatio n between estrogen receptor status and levels of nuclear NF-kappa B complex es. Transcripts of NF-kappa B-regulated genes were found elevated in breast tumors, as compared to adjacent normal tissue, indicating functional NF-ka ppa B activity. These data suggest a potential role for a subset of NF-kapp a B and I kappa-B family proteins, particularly NF-kappa B/p52 and Bcl-3, i n human breast cancer. Additionally, the activation of functional NF-kappa B in these tumors likely involves a signal transduction pathway distinct fr om that utilized by cytokines.