350 rub
Journal №8 for 2011 г.
Article in number:
Comparative immunoenzymatic study of nuclear transcription factor NF-κB, its inhibitor IκBα, and upstream effector protein kinase Akt1 expression and activity in the tumors of breast cancer patients
Authors:
N.E. Kushlinsky, E.S. Gershtein, A.M. Scherbakov, A.M. Platova, G.Yu. Tchemeris, E.V. Oshkina, A.A. Tuleuova, V.P. Letyagin
Abstract:
A coordinate increase of nuclear transcription factor NF-κB p65 and p50 subunits - DNA binding activities was demonstrated by quantitative immunoenzymatic methods in more than 90 % of breast cancers samples as compared to adjacent histologically unchanged mammary gland tissue. An association with total protein content increase was demonstrated for NF-kBp65 DNA binding. The activities of both NF-kB subunits were positively associated with the contents NF-kB inhibitor IkBa and effector protein kinase Akt1 that were also elevated in the majority of the tumors. NF-kBp50 activity was several times higher than that of NF-kBp65 and correlated with the level of activated (phosphorilated) Akt1 that was increased in only 37 % of the tumors. No significant associations were revealed between the parameters studied and main breast cancer clinico-pathologic characteristics including steroid hormone receptors and HER2/neu status.
Pages: 56-61
References
  1. Biswas D.K., Shi Q., Baily S., Strickland I., Ghosh S., Pardee A.B., Iglehart J.D. NF-kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis // Proc. Natl. Acad. Sci. USA. 2004. V. 101. № 27. P. 10137-10142.
  2. Adli M., Baldwin A.S. IKK-i/IKKepsilon controls constitutive, cancer cell-associated NF-kappaB activity via regulation of Ser-536 p65/RelA phosphorylation // J. Biol. Chem. 2006. V. 281. № 37. P. 26976-26984.
  3. Bhat-Nakshatri P., Sweeney C.J., Nakshatri H. Identification of signal transduction pathways involved in constitutive NF-kappaB activation in breast cancer cells // Oncogene. 2002. V. 21. № 13. P. 2066-2078.
  4. Baldwin A.S. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB // J. Clin. Invest. 2001. V. 107. № 3. P. 241-246.
  5. Герштейн Е.С., Овчинникова Л.К., Кушлинский Н.Е. Роль ядерного транскрипционного фактора NF-kappa B в этиологии, патогенезе и клиническом течении рака молочной железы // Вопросы биологической, медицинской и фармацевтической химии. 2009. № 5. С. 10-13.
  6. Ahmed K.M., Cao N., Li J.J. HER-2 and NF-kappaB as the targets for therapy-resistant breast cancer // Anticancer Res. 2006. V. 26. № 6B. P. 4235-4243.
  7. Zhou Y., Eppenberger-Castori S., Eppenberger U., Benz C.C. The NFkappaB pathway and endocrine-resistant breast cancer // Endocr. Relat. Cancer. 2005. V. 12. Suppl.1. P. 37-46. 
  8. Russo S.M., Tepper J.E., Baldwin A.S.Jr., Liu R., Adams J., Elliott P., Cusack J.C.Jr. Enhancement of radiosensitivity by proteasome inhibition: implications for a role of NF-kappaB // Int. J. Radiat. Oncol. Biol. Phys. 2001. V. 50. № 1. P. 183-193.
  9. Biswas D.K., Iglehart J.D. Linkage between EGFR family receptors and nuclear factor kappaB (NF-kappaB) signaling in breast cancer // J. Cell. Physiol. 2006. V. 209. № 3. P. 645-652.
  10. Biswas D.K., Cruz A.P., Gansberger E., Pardee A.B. Epidermal growth factor-induced nuclear factor kappa B activation: A major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells // Proc. Natl. Acad. Sci. USA. 2000. V. 97. № 15. P. 8542-8547.
  11. Zhou Y., Eppenberger-Castori S., Marx C., Yau C., Scott G.K., Eppenberger U., Benz C.C. Activation of nuclear factor-kappaB (NFkappaB) identifies a high-risk subset of hormone-dependent breast cancers // Int. J. Biochem. Cell. Biol. 2005. V. 37. № 5. P. 1130-1144.
  12. Zhou Y., Yau C., Gray J.W., Chew K., Dairkee S.H., Moore D.H., Eppenberger U., Eppenberger-Castori S., Benz C.C. Enhanced NF kappa B and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer // BMC Cancer. 2007. V. 7. P. 59.
  13. Park B.K., Zhang H., Zeng Q., Dai J., Keller E.T., Giordano T., Gu K., Shah V., Pei L., Zarbo R.J. et al. NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF // Nat. Med. 2007. V. 13. № 1. P. 62-69.
  14. Wu J.T., Kral J.G. The NF-kappaB/IkappaB signaling system: a molecular target in breast cancer therapy // J. Surg. Res. 2005. V. 123. № 1. P. 158-169.
  15. Cogswell P.C., Guttridge D.C., Funkhouser W.K., Baldwin A.S.Jr. Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3 // Oncogene. 2000. V. 19. № 9. P. 1123-1131.
  16. Van Laere S.J., Van der Auwera I., Van den Eynden G.G., van Dam P., Van Marck E.A., Vermeulen P.B., Dirix L.Y. NF-kappaB activation in inflammatory breast cancer is associated with oestrogen receptor downregulation, secondary to EGFR and/or ErbB2 overexpression and MAPK hyperactivation // Br. J. Cancer. 2007. V. 97. № 5. P. 659-669.
  17. Gershtein E.S., Scherbakov A.M., Shatskaya V.A., Kushlinsky N.E., Krasil'nikov M.A. Phosphatidylinositol 3-kinase/AKT signalling pathway components in human breast cancer: clinicopathological correlations // Anticancer Res. 2007. V. 27. № 4A. P. 1777-1782.
  18. Gershtein E.S., Scherbakov A.M., Anurova O.A., Krasilnikov M.A., Kushlinsky N.E. Phosphorylated Akt1 in human breast cancer measured by direct sandwich enzyme-linked immunosorbent assay: Correlation with clinicopathological features and tumor VEGF-signaling system component levels // Int. J. Biol. Markers. 2006. V. 21. № 1. P. 12-19.