Mouse models of adrenocortical tumors

Abstract

The molecular basis of the organogenesis, homeostasis, and tumorigenesis of the adrenal cortex has been the subject of intense study for many decades. Specifically, characterization of tumor predisposition syndromes with adrenocortical manifestations and molecular profiling of sporadic adrenocortical tumors have led to the discovery of key molecular pathways that promote pathological adrenal growth. However, given the observational nature of such studies, several important questions regarding the molecular pathogenesis of adrenocortical tumors have remained. This review will summarize naturally occurring and genetically engineered mouse models that have provided novel tools to explore the molecular and cellular underpinnings of adrenocortical tumors. New paradigms of cancer initiation, maintenance, and progression that have emerged from this work will be discussed.

Keywords: Adrenal cortex; Adrenal hyperplasia; Adrenal tumor model; Adrenocortical carcinoma; Gonadectomy-induced tumorigenesis; Spontaneous adrenal tumor.

Figure 1. Tools available for the generation of future mouse models of adrenocortical tumors

(Left) Schematic representation shows the architecture of the normal mouse adrenal gland including the outer adrenal capsule and the inner cortex that is comprised of the zona glomerulosa (zG) and the zona fasciculata (zF). Additionally, the X-zone/fetal zone persists until puberty in male mice and pregnancy in female mice. (Right) Several gene promoters and Cre drivers with zone-specific activity are available to target different regions of the adrenal gland. Reporter strains further allow tracking of specific populations within these potential models.