Volume 16 Supplement 1

Abstracts from the 7th International Conference on cGMP Generators, Effectors and Therapeutic Implications

Open Access

Cyclic GMP Dependent Protein Kinase (PKG) as a mediator of EGFR-Induced Apoptosis in Breast Cancer

BMC Pharmacology and Toxicology201516(Suppl 1):A60

https://doi.org/10.1186/2050-6511-16-S1-A60

Published: 2 September 2015

Background

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase with critical implications in cell proliferation, migration, wound healing and the regulation of apoptosis. However, the EGFR has been shown to be hyper-expressed in a number of human malignancies. The MDA-MB-468 metastatic breast cell line is one example of this. This particular cell line hyper-expresses the EGFR and undergoes EGFR mediated apoptosis in response to EGF ligand. Previous studies within our laboratory have shown that when the EGFR is activated and retained at the cell membrane, MDA-MB-468 cells undergo cell growth. Conversely, once the activated EGFR is internalized within endosomes, the cells undergo apoptosis [1]. This contrasting response at subcellular locations is defined as spatial regulation. The goal of this project is to identify the kinases responsible for the induction of apoptosis from within the endosomes. Research has shown that cGMP dependent protein kinase (PKG) activation within this cell line induces apoptosis in a dose dependent manner [2]. We hypothesize that PKG plays an intermediate role in the EGFR induction of apoptosis.

Conclusion

The data confirm that PKG activation induces cell death within the MDA-MB-468 cell line. PKG activity is also correlated to, and downstream of EGFR activation. Future studies entail inhibiting PKG activity in order to determine its individual role in mediating EGFR-induced apoptosis.

Authors’ Affiliations

(1)
Department of Pharmacology and Toxicology, University of Louisville

References

  1. Hyatt DC, Ceresa BP: Cellular localization of the activated EGFR determines its effect on cell growth in MDA-MB-468 cells. Exp Cell Res. 2008, 314 (18): 3415-3425. 10.1016/j.yexcr.2008.08.020.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Fallahian F, Karami-Tehrani F, Salami S, Aghaei M: Cyclic GMP induced apoptosis via protein kinase G in oestrogen receptor-positive and -negative breast cancer cell lines. FEBS J. 2011, 278 (18): 3360-3369. 10.1111/j.1742-4658.2011.08260.x.View ArticlePubMedGoogle Scholar

Copyright

© Jackson and Ceresa 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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