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Treatment with Angiotensin-(1-7) Prevents Development of Oral Papilloma Induced in K-ras Transgenic Mice
- Oral Squamous Cell Carcinoma (OSCC) is the most common malignant cancer affecting the oral cavity. It is characterized by high morbidity and very few therapeutic options. Angiotensin (Ang)-(1-7) is a biologically active heptapeptide, generated predominantly from AngII (Ang-(1-8)) by the enzymatic activity of angiotensin-converting enzyme 2 (ACE 2). Previous studies have shown that Ang-(1-7) counterbalances AngII pro-tumorigenic actions in different pathophysiological settings, exhibiting antiproliferative and anti-angiogenic properties in cancer cells. However, the prevailing effects of Ang-(1-7) in the oral epithelium have not been established in vivo. Here, we used an inducible oral-specific mouse model, where the expression of a tamoxifen-inducible Cre recombinase (CreERtam), which is under the control of the cytokeratin 14 promoter (K14-CreERtam), induces the expression of the K-ras oncogenic variant KrasG12D (LSLK-rasG12D). These mice develop highly proliferative squamous papilloma in the oral cavity and hyperplasia exclusively in oral mucosa within one month after tamoxifen treatment. Ang-(1-7) treated mice showed a reduced papilloma development accompanied by a significant reduction in cell proliferation and a decrease in pS6 positivity, the most downstream target of the PI3K/Akt/mTOR signaling route in oral papilloma. These results suggest that Ang-(1-7) may be a novel therapeutic target for OSCC.
Author: | Carolina Schere-Levy, Melisa Suberbordes, Darío M. Ferri, Marina Ayre, Albana Gattelli, Edith C. Kordon, Ana R. Raimondi, Thomas Walther |
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URN: | urn:nbn:de:gbv:9-opus-64556 |
DOI: | https://doi.org/10.3390/ijms23073642 |
ISSN: | 1422-0067 |
Parent Title (English): | International Journal of Molecular Sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Editor: | Diego La Mendola, Maria Letizia Trincavelli, Claudia Martini |
Document Type: | Article |
Language: | English |
Date of first Publication: | 2022/03/26 |
Release Date: | 2022/11/15 |
Tag: | Ang-(1-7); K-ras; mTor; oral cancer; papilloma; tumor |
GND Keyword: | - |
Volume: | 23 |
Issue: | 7 |
Faculties: | Universitätsmedizin / Institut für Pharmakologie |
Licence (German): | Creative Commons - Namensnennung |