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Influence of novel KGFR tyrosine kinase inhibitors on KGF-mediated proliferation of breast cancer.
Anticancer Res. 2010 Dec; 30(12):4883-9.AR

Abstract

BACKGROUND

Keratinocyte growth factor (KGF) acts at the KGF receptor (KGFR) to produce a rapid stimulation of breast cancer cell proliferation and motility which is mediated via the Erk signaling pathway. Enhancement of KGF/KGFR signal transduction may be an early step in the metastatic progression of breast cancer. Receptor modeling of KGFR was used to identify selective KGFR tyrosine kinase (TK) inhibitor molecules that have the potential to bind selectively to the KGFR. The present study evaluated the biological activity of 57 of these KGFR TK inhibitor compounds on breast cancer cells.

MATERIALS AND METHODS

These compounds were tested for their ability to inhibit KGF-mediated breast cancer cell proliferation in MCF-7 breast cancer cells. Furthermore, the effects of the most effective proliferation inhibitors were examined on Erk signaling and on the relative density of cell membrane KGFR.

RESULTS

It was observed that 27 of the 57 compounds tested produced a 20% or greater reduction in KGF-mediated proliferation; while five compounds produced greater than 50% inhibition. In addition, the most potent inhibitors also reduced Erk signaling and cell membrane density of the KGFR.

CONCLUSION

The compounds examined appear to be selective KGFR inhibitors which inhibit KGF-mediated activity and reduce the expression of KGFR on cancer cells. These results may lead to the development of a novel class of anticancer agents for the prevention of metastatic cancer progression.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21187466

Citation

Mehta, Meghna, et al. "Influence of Novel KGFR Tyrosine Kinase Inhibitors On KGF-mediated Proliferation of Breast Cancer." Anticancer Research, vol. 30, no. 12, 2010, pp. 4883-9.
Mehta M, Kesinger JW, Zang XP, et al. Influence of novel KGFR tyrosine kinase inhibitors on KGF-mediated proliferation of breast cancer. Anticancer Res. 2010;30(12):4883-9.
Mehta, M., Kesinger, J. W., Zang, X. P., Lerner, M. L., Brackett, D. J., Brueggemeier, R. W., Li, P. K., & Pento, J. T. (2010). Influence of novel KGFR tyrosine kinase inhibitors on KGF-mediated proliferation of breast cancer. Anticancer Research, 30(12), 4883-9.
Mehta M, et al. Influence of Novel KGFR Tyrosine Kinase Inhibitors On KGF-mediated Proliferation of Breast Cancer. Anticancer Res. 2010;30(12):4883-9. PubMed PMID: 21187466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of novel KGFR tyrosine kinase inhibitors on KGF-mediated proliferation of breast cancer. AU - Mehta,Meghna, AU - Kesinger,Jason W, AU - Zang,Xiao-Ping, AU - Lerner,Megan L, AU - Brackett,Daniel J, AU - Brueggemeier,Robert W, AU - Li,Pui-Kui, AU - Pento,J Thomas, PY - 2010/12/29/entrez PY - 2010/12/29/pubmed PY - 2011/2/5/medline SP - 4883 EP - 9 JF - Anticancer research JO - Anticancer Res VL - 30 IS - 12 N2 - BACKGROUND: Keratinocyte growth factor (KGF) acts at the KGF receptor (KGFR) to produce a rapid stimulation of breast cancer cell proliferation and motility which is mediated via the Erk signaling pathway. Enhancement of KGF/KGFR signal transduction may be an early step in the metastatic progression of breast cancer. Receptor modeling of KGFR was used to identify selective KGFR tyrosine kinase (TK) inhibitor molecules that have the potential to bind selectively to the KGFR. The present study evaluated the biological activity of 57 of these KGFR TK inhibitor compounds on breast cancer cells. MATERIALS AND METHODS: These compounds were tested for their ability to inhibit KGF-mediated breast cancer cell proliferation in MCF-7 breast cancer cells. Furthermore, the effects of the most effective proliferation inhibitors were examined on Erk signaling and on the relative density of cell membrane KGFR. RESULTS: It was observed that 27 of the 57 compounds tested produced a 20% or greater reduction in KGF-mediated proliferation; while five compounds produced greater than 50% inhibition. In addition, the most potent inhibitors also reduced Erk signaling and cell membrane density of the KGFR. CONCLUSION: The compounds examined appear to be selective KGFR inhibitors which inhibit KGF-mediated activity and reduce the expression of KGFR on cancer cells. These results may lead to the development of a novel class of anticancer agents for the prevention of metastatic cancer progression. SN - 1791-7530 UR - https://www.unboundmedicine.com/medline/citation/21187466/Influence_of_novel_KGFR_tyrosine_kinase_inhibitors_on_KGF_mediated_proliferation_of_breast_cancer_ L2 - http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=21187466 DB - PRIME DP - Unbound Medicine ER -