PAD2 overexpression in transgenic mice augments malignancy and tumor-associated inflammation in chemically initiated skin tumors.
Cell Tissue Res
; 370(2): 275-283, 2017 11.
Article
en En
| MEDLINE
| ID: mdl-28766045
ABSTRACT
We previously found that transgenic mice overexpressing MMTV-FLAG-hPAD2 (PAD2OE) developed spontaneous skin lesions, with a subset of these lesions progressing to invasive squamous cell carcinoma (SCC). The goal of this report was to better understand the potential mechanisms by which PAD2 overexpression promotes skin cancer. Here, PAD2OE mice were treated with the carcinogen, 9,10-dimethyl-1,2-benzanthracene and with O-tetradecanoylphorbol-13-acetate and then scored for papilloma formation. Additionally, tumor sections were evaluated for evidence of tumor cell invasion and inflammation. We found that the total number of papillomas was significantly increased in PAD2OE mice compared to controls. Histopathologic analysis of the lesions found that in PAD2OE skin tumors progressed to invasive SCC more frequently than controls. Additionally, we found that PAD2OE lesions were highly inflamed, with a dense inflammatory cell infiltrate and an associated increase in nuclear phospho-STAT3 (signal transducer and activator of transcription 3) in the transgenic tumors. These data suggest that overexpression of the hPAD2 transgene in the epidermis increases the malignant conversion rate of benign tumors by promoting an inflammatory microenvironment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Papiloma
/
Neoplasias Cutáneas
/
Regulación hacia Arriba
/
Desiminasas de la Arginina Proteica
/
Inflamación
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Tissue Res
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos