Paget's disease of the nipple in a Her2-positive breast cancer xenograft model.
Breast Cancer Res Treat
; 179(3): 577-584, 2020 Feb.
Article
de En
| MEDLINE
| ID: mdl-31720992
ABSTRACT
PURPOSE:
Paget's disease (PD) of the breast is an uncommon disease of the nipple usually accompanied by an underlying carcinoma, often HER2 + , and accounting for 0.5-5% of all breast cancer. To date, histogenesis of PD of the breast remains controversial, as two theories-transformation and epidermotropic-have been proposed to explain this disease. Currently, animal models recapitulating PD of the nipple have not been described.METHODS:
HER2-enriched DT13 breast cancer cells were injected into the mammary fat pad of NOD scid gamma null (NSG) female mice. Immunohistochemical staining and pathological studies were performed on tumor samples, and diagnosis of PD of the nipple was confirmed by expression of proteins characteristic of Paget cells (epidermal growth factor 2 (HER2), androgen receptor (AR), cytokeratin 7 (CK7), cytokeratin 8/18 (CK8/18), and mucin 1 (MUC1)). In addition, DT13 cells grown in 2D culture and in soft agar assays were sensitive to in vitro treatment with pharmacological inhibitors targeting Her2, adenylyl cyclase, mTOR, and PI3K signaling pathways.RESULTS:
Mice developed tumors and nipple lesions that were detected exclusively on the tumor-bearing mammary fat pad. Tumor cells were positive for proteins characteristic of Paget cells. In vitro, DT13 cells were sensitive to inhibition of Her2, adenylyl cyclase, mTOR, and PI3K signaling pathways.CONCLUSIONS:
Our results suggest that injection of HER2 + DT13 cells into the mammary fat pad of NSG mice recapitulates critical aspects of the pathophysiology of PD of the nipple, supporting the epidermotropic theory as the more likely to explain the histogenesis of this disease.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du sein
/
Maladie de Paget du sein
/
Récepteur ErbB-2
/
Glandes mammaires animales
/
Mamelons
Type d'étude:
Prognostic_studies
Limites:
Aged
/
Animals
/
Female
/
Humans
Langue:
En
Journal:
Breast Cancer Res Treat
Année:
2020
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique