COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer
Garg R, Blando JM, Perez CJ, Lal P, Feldman MD, Smyth EM, Ricciotti E, Grosser T, Benavides F, Kazanietz MG (2018)
Oncogene 37(34): 4735-4749.
Zeitschriftenaufsatz
| Veröffentlicht | Englisch
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Autor*in
Garg, Rachana;
Blando, Jorge M.;
Perez, Carlos J.;
Lal, Priti;
Feldman, Michael D.;
Smyth, Emer M.;
Ricciotti, Emanuela;
Grosser, TiloUniBi
;
Benavides, Fernando;
Kazanietz, Marcelo G.
![](https://pub.uni-bielefeld.de/images/icon_orcid.png)
Abstract / Bemerkung
The pro-oncogenic kinase PKCε is overexpressed in human prostate cancer and cooperates with loss of the tumor suppressor Pten for the development of prostatic adenocarcinoma. However, the effectors driving PKCε-mediated phenotypes remain poorly defined. Here, using cellular and mouse models, we showed that PKCε overexpression acts synergistically with Pten loss to promote NF-κB activation and induce cyclooxygenase-2 (COX-2) expression, phenotypic traits which are also observed in human prostate tumors. Targeted disruption of PKCε from prostate cancer cells impaired COX-2 induction and PGE2 production. Notably, COX-2 inhibitors selectively killed prostate epithelial cells overexpressing PKCε, and this ability was greatly enhanced by Pten loss. Long-term COX-2 inhibition markedly reduced adenocarcinoma formation, as well as angiogenesis in a mouse model of prostate-specific PKCε expression and Pten loss. Overall, our results provide strong evidence for the involvement of the canonical NF-κB pathway and its target gene COX2 as PKCε effectors, and highlight the potential of PKCε as a useful biomarker for the use of COX inhibition for chemopreventive and/or chemotherapeutic purposes in prostate cancer.
Erscheinungsjahr
2018
Zeitschriftentitel
Oncogene
Band
37
Ausgabe
34
Seite(n)
4735-4749
ISSN
0950-9232
eISSN
1476-5594
Page URI
https://pub.uni-bielefeld.de/record/2965308
Zitieren
Garg R, Blando JM, Perez CJ, et al. COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer. Oncogene. 2018;37(34):4735-4749.
Garg, R., Blando, J. M., Perez, C. J., Lal, P., Feldman, M. D., Smyth, E. M., Ricciotti, E., et al. (2018). COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer. Oncogene, 37(34), 4735-4749. https://doi.org/10.1038/s41388-018-0318-9
Garg, Rachana, Blando, Jorge M., Perez, Carlos J., Lal, Priti, Feldman, Michael D., Smyth, Emer M., Ricciotti, Emanuela, Grosser, Tilo, Benavides, Fernando, and Kazanietz, Marcelo G. 2018. “COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer”. Oncogene 37 (34): 4735-4749.
Garg, R., Blando, J. M., Perez, C. J., Lal, P., Feldman, M. D., Smyth, E. M., Ricciotti, E., Grosser, T., Benavides, F., and Kazanietz, M. G. (2018). COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer. Oncogene 37, 4735-4749.
Garg, R., et al., 2018. COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer. Oncogene, 37(34), p 4735-4749.
R. Garg, et al., “COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer”, Oncogene, vol. 37, 2018, pp. 4735-4749.
Garg, R., Blando, J.M., Perez, C.J., Lal, P., Feldman, M.D., Smyth, E.M., Ricciotti, E., Grosser, T., Benavides, F., Kazanietz, M.G.: COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer. Oncogene. 37, 4735-4749 (2018).
Garg, Rachana, Blando, Jorge M., Perez, Carlos J., Lal, Priti, Feldman, Michael D., Smyth, Emer M., Ricciotti, Emanuela, Grosser, Tilo, Benavides, Fernando, and Kazanietz, Marcelo G. “COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer”. Oncogene 37.34 (2018): 4735-4749.
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