Volume 76, Issue 1 p. 80-96
Original Article

Notch signaling dynamics in the adult healthy prostate and in prostatic tumor development

Ana-Rita Pedrosa

Ana-Rita Pedrosa

Centro Interdisciplinar de Investigação em Sanidade Animal (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal

Search for more papers by this author
José L. Graça

José L. Graça

Centro Interdisciplinar de Investigação em Sanidade Animal (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal

Search for more papers by this author
Sandra Carvalho

Sandra Carvalho

Centro Interdisciplinar de Investigação em Sanidade Animal (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal

Search for more papers by this author
Maria C. Peleteiro

Maria C. Peleteiro

Centro Interdisciplinar de Investigação em Sanidade Animal (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal

Search for more papers by this author
António Duarte

António Duarte

Centro Interdisciplinar de Investigação em Sanidade Animal (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal

Instituto Gulbenkian de Ciência, Oeiras, Portugal

Search for more papers by this author
Alexandre Trindade

Corresponding Author

Alexandre Trindade

Centro Interdisciplinar de Investigação em Sanidade Animal (CIISA), Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal

Instituto Gulbenkian de Ciência, Oeiras, Portugal

Correspondence to: Alexandre Trindade, Faculdade de Medicina Veterinária, Av. Universidade Técnica, 1300-477 Lisboa, Portugal. E-mail: [email protected]

Search for more papers by this author
First published: 30 September 2015
Citations: 20
Ana-Rita Pedrosa and José L. Graça contributed equally to this work.
Conflict of interest: None.

Abstract

BACKGROUND

The Notch signaling pathway has been implicated in prostate development, maintenance and tumorigenesis by its key role in cell-fate determination, differentiation and proliferation. Therefore, we proposed to analyze Notch family members transcription and expression, including ligands (Dll1, 3, 4 and Jagged1 and 2), receptors (Notch1–4) and effectors (Hes1, 2, 5 and Hey1, 2, L), in both normal and tumor bearing mouse prostates to better understand the dynamics of Notch signaling in prostate tumorigenesis.

METHODS

Wild type mice and transgenic adenocarcinoma of the mouse prostate model (TRAMP) mice were sacrificed at 18, 24 or 30 weeks of age and the prostates collected and processed for either whole prostate or prostate cell specific populations mRNA analysis and for protein expression analysis by immunohistochemistry and immunofluorescence.

RESULTS

We observed that Dll1 and Dll4 are expressed in the luminal compartment of the mouse healthy prostate, whereas Jagged2 expression is restricted to the basal and stromal compartment. Additionally, Notch2 and Notch4 are normally expressed in the prostate luminal compartment while Notch2 and Notch3 are also expressed in the stromal layer of the healthy prostate. As prostate tumor development takes place, there is up-regulation of Notch components. Particularly, the prostate tumor lesions have increased expression of Jagged1 and 2, of Notch3 and of Hey1. We have also detected the presence of activated Notch3 in prostatic tumors that co-express Jagged1 and ultimately the Hey1 effector.

CONCLUSIONS

Taken together our results point out the Notch axis Jagged1-2/Notch3/Hey1 to be important for prostate tumor development and worthy of additional functional studies and validation in human clinical disease. Prostate 76:80–96, 2016. © 2015 Wiley Periodicals, Inc.

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.