Identification and characterization of poorly differentiated invasive carcinomas in a mouse model of pancreatic neuroendocrine tumorigenesis

Pancreatic neuroendocrine tumors (PanNETs) are a relatively rare but clinically challenging tumor type. In particular, high grade, poorly-differentiated PanNETs have the worst patient prognosis, and the underlying mechanisms of disease are poorly understood. In this study we have identified and char...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2013-05, Vol.8 (5), p.e64472
Main Authors: Hunter, Karen E, Quick, Marsha L, Sadanandam, Anguraj, Hanahan, Douglas, Joyce, Johanna A
Format: Article
Language:English
Subjects:
Analysis
Animals
Antigens
Beta cells
Biology
Biomarkers, Tumor - metabolism
Cancer
Carcinogenesis
Carcinoma
Carcinoma, Neuroendocrine - genetics
Carcinoma, Neuroendocrine - metabolism
Carcinoma, Neuroendocrine - pathology
Cell differentiation
Deoxyribonucleic acid
Differentiation (biology)
Disease Models, Animal
DNA
Gene expression
Gene Expression Regulation, Neoplastic
Genetics
Growth factors
Id1 protein
Identification
Inhibitor of Differentiation Protein 1 - genetics
Insulin
Life sciences
Medical prognosis
Medical research
Medicine
Metastasis
Mice
Mitosis
Movement disorders
Neoplasm Invasiveness
Neurodegenerative diseases
Neuroendocrine tumors
Pancreas
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Parkinson's disease
Prognosis
Rodents
Tumor cells
Tumorigenesis
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pancreatic neuroendocrine tumors (PanNETs) are a relatively rare but clinically challenging tumor type. In particular, high grade, poorly-differentiated PanNETs have the worst patient prognosis, and the underlying mechanisms of disease are poorly understood. In this study we have identified and characterized a previously undescribed class of poorly differentiated PanNETs in the RIP1-Tag2 mouse model. We found that while the majority of tumors in the RIP1-Tag2 model are well-differentiated insulinomas, a subset of tumors had lost multiple markers of beta-cell differentiation and were highly invasive, leading us to term them poorly differentiated invasive carcinomas (PDICs). In addition, we found that these tumors exhibited a high mitotic index, resembling poorly differentiated (PD)-PanNETs in human patients. Interestingly, we identified expression of Id1, an inhibitor of DNA binding gene, and a regulator of differentiation, specifically in PDIC tumor cells by histological analysis. The identification of PDICs in this mouse model provides a unique opportunity to study the pathology and molecular characteristics of PD-PanNETs.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0064472