Animal models of adrenocortical tumorigenesis

Abstract

Over the past decade, research on human adrenocortical neoplasia has been dominated by gene expression profiling of tumor specimens and by analysis of genetic disorders associated with a predisposition to these tumors. Although these studies have identified key genes and associated signaling pathways that are dysregulated in adrenocortical neoplasms, the molecular events accounting for the frequent occurrence of benign tumors and low rate of malignant transformation remain unknown. Moreover, the prognosis for patients with adrenocortical carcinoma remains poor, so new medical treatments are needed. Naturally occurring and genetically engineered animal models afford a means to investigate adrenocortical tumorigenesis and to develop novel therapeutics. This comparative review highlights adrenocortical tumor models useful for either mechanistic studies or preclinical testing. Three model species - mouse, ferret, and dog - are reviewed, and their relevance to adrenocortical tumors in humans is discussed.

Figure 1

(A) Ferret with symmetrical alopecia due to adrenocortical neoplasia. (B-E) Histological appearance of ferret adrenocortical neoplasms. Adrenocortical adenoma (A,B) or myxoid adrenocortical carcinoma (C,D) stained with H&E (A,C) or GATA4 antibody (avidin-biotin complex peroxidase method) (B,D). The arrowhead highlights the spindle cell component of the tumor. Bars = 100 μm.

Figure 2

(A) Dog with typical clinical signs of Cushing's syndrome: abdominal obesity, muscle atrophy, thin skin and fatigue. (B) The same dog after treatment.