In mammals and other tetrapods, a multinuclear forebrain structure, called the amygdala, forms the neuroregulatory core essential for emotion, cognition, and social behavior. Currently, higher circuits of affective behavior in anamniote non-tetrapod vertebrates (“fishes”) are poorly understood, preventing a comprehensive understanding of amygdala evolution. Through molecular characterization and evolutionary-developmental considerations, we delineated the complex amygdala ground plan of zebrafish, whose everted telencephalon has made comparisons to the evaginated forebrains of tetrapods challenging. In this radical paradigm, thirteen telencephalic territories constitute the zebrafish amygdaloid complex and each territory is distinguished by conserved molecular properties and structure-functional relationships with other amygdaloid structures. Central to our paradigm, the study identifies the teleostean amygdaloid nucleus of the lateral olfactory tract (nLOT), an olfactory integrative structure that links dopaminergic telencephalic groups to the amygdala alongside redefining the putative zebrafish olfactory pallium (“Dp”). Molecular characteristics such as the distribution of substance P and the calcium-binding proteins parvalbumin (PV) and calretinin (CR) indicate, that the zebrafish extended centromedial (autonomic and reproductive) amygdala is predominantly located in the GABAergic and isl1-negative territory. Like in tetrapods, medial amygdaloid (MeA) nuclei are defined by the presence of substance P immunoreactive fibers and calretinin-positive neurons, whereas central amygdaloid (CeA) nuclei lack these characteristics. A detailed comparison of lhx5-driven and vGLut2a-driven GFP in transgenic reporter lines revealed ancestral topological relationships between the thalamic eminence (EmT), the medial amygdala (MeA), the nLOT, and the integrative olfactory pallium. Thus, the study explains how the zebrafish amygdala and the complexly everted telencephalon topologically relate to the corresponding structures in mammals indicating that an elaborate amygdala ground plan evolved early in vertebrates, in a common ancestor of teleosts and tetrapods.

The nuclear receptor superfamily comprises a large group of proteins with functions essential for cell signaling, survival, and proliferation. There are multiple distinctions between nuclear superfamily classes defined by hallmark differences in function, ligand binding, tissue specificity, and DNA binding. In this review, we utilize the initial classification system, which defines subfamilies based on structure and functional difference. The defining feature of the nuclear receptor superfamily is that these proteins function as transcription factors. The loss of transcriptional regulation or gain of functioning of these receptors is a hallmark in numerous diseases. For example, in prostate cancer, the androgen receptor is a primary target for current prostate cancer therapies. Targeted cancer therapies for nuclear hormone receptors have been more feasible to develop than others due to the ligand availability and cell permeability of hormones. To better target these receptors, it is critical to understand their structural and functional regulation. Given that late-stage cancers often develop hormone insensitivity, we will explore the strengths and pitfalls of targeting other transcription factors outside of the nuclear receptor superfamily such as the signal transducer and activator of transcription (STAT).

Estrogen receptor-positive (ER+) invasive lobular breast cancer (ILC) comprises about ~15% of breast cancer. ILC’s unique genotypic (loss of wild type E-cadherin expression) and phenotypic (small individual round cancer cells that grow in discontinuous nests) are thought to contribute to a distinctive pattern of metastases to serosal membranes. Unlike invasive ductal carcinoma (IDC), ILC metastases often intercalate into the mesothelial layer of the peritoneum and other serosal surfaces. While ER activity is a known driver of ILC proliferation, very little is known about how additional nuclear receptors contribute to ILC’s distinctive biology. In ER+ IDC, we showed previously that glucocorticoid receptor (GR) activity inhibits pro-proliferative gene expression and cell proliferation. Here we examined ER+ ILC models and found that GR activation similarly reduces S-phase entry gene expression and ILC proliferation. While slowing tumor growth rate, our data also suggest that GR activation results in an enhanced metastatic phenotype through increasing integrin-encoding gene expression, extracellular matrix protein adhesion, and mesothelial cell clearance. Moreover, in an intraductal mouse mammary gland model of ILC, we found that GR expression is associated with increased bone metastases despite slowed primary mammary tumor growth. Taken together, our findings suggest GR-mediated gene expression may contribute to the unusual characteristics of ILC biology.

In 2022, prostate cancer (PCa) is estimated to be the most commonly diagnosed cancer in men in the United States—almost 270,000 American men are estimated to be diagnosed with PCa in 2022. This review compares and contrasts in vivo models of PCa with regards to the altered genes, signaling pathways, and stages of tumor progression associated with each model. The main type of model included in this review are genetically engineered mouse models, which include conditional and constitutive knockout model. 2D cell lines, 3D organoids and spheroids, xenografts and allografts, and patient derived models are also included. The major applications, advantages and disadvantages, and ease of use and cost are unique to each type of model, but they all make it easier to translate the tumor progression that is seen in the mouse prostate to the human prostate. Although both human and mouse prostates are androgen-dependent, the fact that the native, genetically unaltered prostate in mice cannot give rise to carcinoma is an especially critical component of PCa models. Thanks to the similarities between the mouse and human genome, our knowledge of PCa has been expanded, and will continue to do so, through models of PCa.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay; however, some patients will transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC may develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, however, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.