Tags

Type your tag names separated by a space and hit enter

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 U S A. 2000 Jul 18; 97(15):8542-7.PN

Abstract

The epidermal growth factor (EGF) family of receptors (EGFR) is overproduced in estrogen receptor (ER) negative (-) breast cancer cells. An inverse correlation of the level of EGFR and ER is observed between ER- and ER positive (+) breast cancer cells. A comparative study with EGFR-overproducing ER- and low-level producing ER+ breast cancer cells suggests that EGF is a major growth-stimulating factor for ER- cells. An outline of the pathway for the EGF-induced enhanced proliferation of ER- human breast cancer cells is proposed. The transmission of mitogenic signal induced by EGF-EGFR interaction is mediated via activation of nuclear factor kappaB (NF-kappaB). The basal level of active NF-kappaB in ER- cells is elevated by EGF and inhibited by anti-EGFR antibody (EGFR-Ab), thus qualifying EGF as a NF-kappaB activation factor. NF-kappaB transactivates the cell-cycle regulatory protein, cyclin D1, which causes increased phosphorylation of retinoblastoma protein, more strongly in ER- cells. An inhibitor of phosphatidylinositol 3 kinase, Ly294-002, blocked this event, suggesting a role of the former in the activation of NF-kappaB by EGF. Go6976, a well-characterized NF-kappaB inhibitor, blocked EGF-induced NF-kappaB activation and up-regulation of cell-cycle regulatory proteins. This low molecular weight compound also caused apoptotic death, predominantly more in ER- cells. Thus Go6976 and similar NF-kappaB inhibitors are potentially novel low molecular weight therapeutic agents for treatment of ER- breast cancer patients.

Authors+Show Affiliations

Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA. biswas@mbcrr.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10900013

Citation

Biswas, D K., et al. "Epidermal Growth Factor-induced Nuclear Factor Kappa B Activation: a Major Pathway of Cell-cycle Progression in Estrogen-receptor Negative Breast Cancer Cells." Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 15, 2000, pp. 8542-7.
Biswas DK, Cruz AP, Gansberger E, et al. 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 U S A. 2000;97(15):8542-7.
Biswas, D. K., Cruz, A. P., Gansberger, E., & Pardee, A. B. (2000). Epidermal growth factor-induced nuclear factor kappa B activation: A major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 97(15), 8542-7.
Biswas DK, et al. 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 U S A. 2000 Jul 18;97(15):8542-7. PubMed PMID: 10900013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epidermal growth factor-induced nuclear factor kappa B activation: A major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells. AU - Biswas,D K, AU - Cruz,A P, AU - Gansberger,E, AU - Pardee,A B, PY - 2000/7/19/pubmed PY - 2000/8/29/medline PY - 2000/7/19/entrez SP - 8542 EP - 7 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 97 IS - 15 N2 - The epidermal growth factor (EGF) family of receptors (EGFR) is overproduced in estrogen receptor (ER) negative (-) breast cancer cells. An inverse correlation of the level of EGFR and ER is observed between ER- and ER positive (+) breast cancer cells. A comparative study with EGFR-overproducing ER- and low-level producing ER+ breast cancer cells suggests that EGF is a major growth-stimulating factor for ER- cells. An outline of the pathway for the EGF-induced enhanced proliferation of ER- human breast cancer cells is proposed. The transmission of mitogenic signal induced by EGF-EGFR interaction is mediated via activation of nuclear factor kappaB (NF-kappaB). The basal level of active NF-kappaB in ER- cells is elevated by EGF and inhibited by anti-EGFR antibody (EGFR-Ab), thus qualifying EGF as a NF-kappaB activation factor. NF-kappaB transactivates the cell-cycle regulatory protein, cyclin D1, which causes increased phosphorylation of retinoblastoma protein, more strongly in ER- cells. An inhibitor of phosphatidylinositol 3 kinase, Ly294-002, blocked this event, suggesting a role of the former in the activation of NF-kappaB by EGF. Go6976, a well-characterized NF-kappaB inhibitor, blocked EGF-induced NF-kappaB activation and up-regulation of cell-cycle regulatory proteins. This low molecular weight compound also caused apoptotic death, predominantly more in ER- cells. Thus Go6976 and similar NF-kappaB inhibitors are potentially novel low molecular weight therapeutic agents for treatment of ER- breast cancer patients. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/10900013/Epidermal_growth_factor_induced_nuclear_factor_kappa_B_activation:_A_major_pathway_of_cell_cycle_progression_in_estrogen_receptor_negative_breast_cancer_cells_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=10900013 DB - PRIME DP - Unbound Medicine ER -