Abstract
Members of the NF-κB/Rel transcription factor family have been shown recently to be required for cellular transformation by oncogenic Ras and by other oncoproteins and to suppress transformation-associated apoptosis. Furthermore, NF-κB has been shown to be activated by several oncoproteins including HER2/Neu, a receptor tyrosine kinase often expressed in human breast 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-κB. Furthermore, RNA levels for NF-κB-activated genes were analysed in order to determine if NF-κB is functionally active in human breast cancer. Our data indicate that the p65/RelA subunit of NF-κB is activated (i.e., nuclear) in breast cancer cell lines. However, breast tumors exhibit an absence or low level of nuclear p65/RelA but show activated c-Rel, p50 and p52 as compared to nontumorigenic adjacent tissue. Additionally, the IκB homolog Bcl-3, which functions to stimulate transcription with p50 or p52, was also activated in breast tumors. There was no apparent correlation between estrogen receptor status and levels of nuclear NF-κB complexes. Transcripts of NF-κB-regulated genes were found elevated in breast tumors, as compared to adjacent normal tissue, indicating functional NF-κB activity. These data suggest a potential role for a subset of NF-κB and IκB family proteins, particularly NF-κB/p52 and Bcl-3, in human breast cancer. Additionally, the activation of functional NF-κB in these tumors likely involves a signal transduction pathway distinct from that utilized by cytokines.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Arsura M, Wu M and Sonenshein GE. . 1996 Immunity 5: 31–40.
Baldwin AS. . 1996 Ann. Rev. Immunol. 14: 649–683.
Bargou RC, Emmerich F, Krappmann D, Bommert K, Mapara MY, Arnold W, Royer HD, Grinstein E, Greiner A, Scheidereit C and Dorken B. . 1997 J. Clin. Invest. 100: 2961–2969.
Beg AA and Baltimore D. . 1996 Science 274: 782–784.
Beg AA, Sha W, Bronson R, Ghosh S and Baltimore D. . 1995 Nature 376: 167–170.
Bours V, Franzoso G, Azarenko V, Park S, Kanno T, Brown K and Siebenlist U. . 1993 Cell 72: 729–739.
Caamano JH, Rizzo CA, Durham SK, Barton DS, Raventos-Suarez C, Snapper CM and Bravo R. . 1998 J. Exp. Med. 187: 185–196.
Cabannes E, Khan G, Aillet F, Jarrett R and Hay R. . 1999 Oncogene 18: 3063–3070.
Carrasco D, Perez P, Lewin A and Bravo R. . 1997 J. Exp. Med. 186: 279–288.
Chang CC, Zhang J, Lombardi L, Neri A and Dalla-Favera R. . 1995 Mol. Cell. Biol. 15: 5180–5187.
Chu Z, McKinsey T, Liu L, Gentry J, Malim M and Ballard D. . 1997 Proc. Nat. Acad. Sci. USA 94: 10057–10062.
Dejardin E, Bonizzi G, Bellahcene A, Castronovo V, Merville M-P and Bours V. . 1995 Oncogene 11: 1835–1841.
Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieu S, Wulczyn F, Scheidereit C and Leutz A. . 1999 Oncogene 18: 3316–3323.
Dickson RB and Lippman ME. . 1995 Endocrine Rev. 16: 559–589.
Finco TS, Westwick JK, Norris JL, Beg AA, Der CJ and Baldwin AS. . 1997 J. Biol. Chem. 272: 24113–24116.
Franzoso G, Carlson L, Scharton-Kersten T, Shores EW, Epstein S, Grinberg A, Tran T, Shacter E, Leonardi A, Anver A, Love P, Sher A and Siebenslist U. . 1997 Immunity 6: 479–490.
Franzoso G, Carlson L, Poljak L, Shores EW, Epstein S, Leonardi A, Grinberg A, Tran T, Scharton-Kersten T, Anver M, Love P, Brown K and Siebenlist U. . 1998 J. Exp. Med. 187: 147–159.
Fujita T, Nolan GP, Liou HC, Scott M and Baltimore D. . 1993 Genes Dev. 7: 1354–1363.
Galang CK, Garcia-Ramirez J, Solski PA, Westwick JK, Der CJ, Neznanov NN, Oshima RG and Hauser CA. . 1996 J. Biol. Chem. 271: 7992–7998.
Ghosh S, May MJ and Kopp EB. . 1998 Ann. Rev. Immunol. 16: 225–260.
Gilmore TD. . 1997 J. Clin. Invest. 100: 2935–2936.
Guttridge D, Albanese C, Reuther J, Pestell R and Baldwin A. . 1999 Mol. Cell. Biol. 19: 5785–5799.
Heissmeyer V, Krappmann D, Wulczyn FG and Schedereit C. . 1999 EMBO J. 18: 4766–4778.
Hinz M, Krappmann D, Eichten A, Heder A, Scheidereit C and Strauss M. . 1999 Mol. Cell. Biol. 19: 2690–2698.
Ishikawa H, Carrasco D, Claudio E, Ryseck RP and Bravo R. . 1997 J. Exp. Med. 186: 999–1014.
Johnson R, Spiegelman B, Hanahan D and Wisdom R. . 1996 Mol. Cell. Biol. 16: 4504–4511.
Kerr L, Duckett C, Wamsley P, Zhang Q, Chiao P, Nabel G, McKeithan T, Baeuerle P and Verma I. . 1992 Genes Dev. 6: 2352–2363.
Langer SJ, Bortner DM, Roussel MF, Sherr CJ and Ostrowski MC. . 1992 Mol. Cell. Biol. 12: 5355–5362.
Liptay S, Schmid RM, Nabel EG and Nabel GJ. . 1994 Mol. Cell. Biol. 14: 7695–7703.
Liu ZG, Hsu H, Goeddel DV and Karin M. . 1996 Cell 87: 565–576.
Mayo MW, Wang C-Y, Cogswell PC, Rogers-Graham KS, Lowe SW, Der C and Baldwin AS. . 1997 Science 278: 1812–1815.
McKeithan T, Takimoto G, Ohno H, Bjorling V, Morgan R, Hecht B, Dube I, Sandberg A and Rowley J. . 1997 Genes, Chrom. Cancer 20: 64–72.
Michaux L, Dierlamm J, Wlodarska I, Bours V, Van den Berghe H and Hagemeijer A. . 1997 Cancer Gen. Cyto. 94: 36–43.
Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet R and Sledge GW. . 1997 Mol. Cell. Biol. 17: 3629–3639.
Ong S, Hackbarth M, Degenstein L, Baunoch D, Anastasi J and McKeithan T. . 1998 Oncogene 16: 2333–2343.
Ohno H, Takimoto G and McKeithan T. . 1990 Cell 60: 991–997.
Resnik JL, Reichart DB, Huey K, Webster NJ and Seely BL. . 1998 Cancer Res. 58: 1159–1164.
Reuther JY, Reuther GW, Cortez D, Pendergast AM and Baldwin AS. . 1998 Genes Dev. 12: 968–981.
Schmid RM, Liptay S, Betts JC and Nabel GJ. . 1994 J. Biol. Chem. 269: 32162–32167.
Schwartz EM, Krimpenfort P, Berns A and Verma IM. . 1997 Genes Dev. 11: 187–197.
Sherr CJ. . 1996 Science 274: 1672–1677.
Sklar MD, Thompson E, Welsh MJ, Liebert M, Harney J, Grossman HB, Smith M and Prochownik EV. . 1991 Mol. Cell. Biol. 11: 3699–3710.
Sovak MA, Bellas RE, Kim DW, Zanieski G, Rogers A, Traish A and Sonenshein GE. . 1997 J. Clin. Invest. 100: 2952–2960.
Van Antwerp DJ, Martin SJ, Kafri T, Green DR and Verma IM. . 1996 Science 274: 787–789.
Verma IM, Stevenson JK, Schwartz EM, Van Antwerp D and Miyamoto S. . 1995 Genes Dev. 9: 2723–2735.
Wang C-Y, Mayo MW and Baldwin AS. . 1996 Science 274: 784–787.
Watanabe N, Iwamura T, Shinoda T and Fujita T. . 1997 EMBO J. 16: 3609–3620.
Zhang Q, DiDonato J, Karin M and McKeithan T. . 1994 Mol. Cell. Biol. 14: 3915–3926.
Acknowledgements
This work was supported by grant (DAMD-17-4053) from the Department of the Army and by NCI grant (CA72771) both to AS Baldwin Jr, and by UNC Breast Cancer SPORE grant CA58223. DC Gutteridge was supported by NIH T32CA09156 and by an American Cancer Society postdoctoral fellowship award. We gratefully acknowledge J Reuther for helpful suggestions on the manuscript and for help on several different procedures. We also thank A Marshall for technical assistance. We also acknowledge the Lineberger Tissue Procurement Facility for providing the tumor specimens. This paper is dedicated to the memories of Majorie Cappione and Anne-Marie Guttridge.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cogswell, P., Guttridge, D., Funkhouser, W. et al. Selective activation of NF-κB subunits in human breast cancer: potential roles for NF-κB2/p52 and for Bcl-3. Oncogene 19, 1123–1131 (2000). https://doi.org/10.1038/sj.onc.1203412
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1203412
Keywords
This article is cited by
-
The chemokine monocyte chemoattractant protein-1/CCL2 is a promoter of breast cancer metastasis
Cellular & Molecular Immunology (2023)
-
Cell plasticity modulation by flavonoids in resistant breast carcinoma targeting the nuclear factor kappa B signaling
Cancer and Metastasis Reviews (2023)
-
Multiple roles for Bcl-3 in mammary gland branching, stromal collagen invasion, involution and tumor pathology
Breast Cancer Research (2022)
-
BCL3 expression is strongly associated with the occurrence of breast cancer relapse under tamoxifen treatment in a retrospective cohort study
Virchows Archiv (2022)
-
Expression of p52, a non-canonical NF-kappaB transcription factor, is associated with poor ovarian cancer prognosis
Biomarker Research (2020)