Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor

Liu, Ning‐Ai; Jiang, Hong; Ben-Shlomo, Anat; Wawrowsky, Kolja; Fan, Xuemo; Lin, Shuo; Melmed, Shlomo

doi:10.1073/pnas.1018091108

Cited by 124 publications

(101 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). The results indicate that use of selective CDK inhibitors may effectively target corticotrope tumor growth and hormonal secretion (Liu et al 2011b). (Amaral et al 2009).…”

Section: Cell Cycle Regulatorsmentioning

confidence: 99%

“…The leading effect of such pathways is cell cycle arrest with a decrease in tumor growth. Interestingly, using a cyclindependent kinase 2 (CDK2)/cyclin E inhibitor in animal models, the ACTH and corticosterone levels were suppressed, and xenografted pituitary tumor growth was restrained (Liu et al 2011b). Red lines/arrows indicate inhibition, whereas green lines/arrows indicate induction.…”

Section: Peroxisome Proliferator-activated Receptor Gamma Ligandsmentioning

confidence: 99%

“…These results motivate the pharmacological assessment of a CDK2/cyclin E inhibitor, R-roscovitine (seliciclib; CYC202) in corticotrope pituitary adenomas. In transgenic POMC-pituitary tumortransforming gene (PTTG (PTTG1)) zebrafish embryos and in a mouse model of ACTH-secreting pituitary adenomas, R-roscovitine suppressed ACTH expression/ production and inhibited tumor growth (Liu et al 2011b). Molecular analyses in vitro and in vivo showed upregulation of p27, p21, and p57 (CDKN1C), and downregulation of cyclin E expression (Fig.…”

Section: Cell Cycle Regulatorsmentioning

confidence: 99%

See 2 more Smart Citations

Treatment of Cushing's disease: a mechanistic update

Cuevas‐Ramos¹,

Fleseriu²

2014

Journal of Endocrinology

View full text Add to dashboard Cite

Cushing's disease (CD) is characterized by an ACTH-producing anterior corticotrope pituitary adenoma. If hypothalamus-pituitary-adrenal (HPA) axis physiology is disrupted, ACTH secretion increases, which in turn stimulates adrenocortical steroidogenesis and cortisol production. Medical treatment plays an important role for patients with persistent disease after surgery, for those in whom surgery is not feasible, or while awaiting effects of radiation. Multiple drugs, with different mechanisms of action and variable efficacy and tolerability for controlling the deleterious effects of chronic glucocorticoid excess, are available. The molecular basis and clinical data for centrally acting drugs, adrenal steroidogenesis inhibitors, and glucocorticoid receptor antagonists are reviewed, as are potential novel molecules and future possible targets for CD treatment. Although progress has been made in the understanding of specific corticotrope adenoma receptor physiology and recent clinical studies have detected improved effects with a combined medical therapy approach, there is a clear need for a more efficacious and better-tolerated medical therapy for patients with CD. A better understanding of the molecular mechanisms in CD and of HPA axis physiology should advance the development of new drugs in the future.

show abstract

“…3). The results indicate that use of selective CDK inhibitors may effectively target corticotrope tumor growth and hormonal secretion (Liu et al 2011b). (Amaral et al 2009).…”

Section: Cell Cycle Regulatorsmentioning

confidence: 99%

Section: Peroxisome Proliferator-activated Receptor Gamma Ligandsmentioning

confidence: 99%

Section: Cell Cycle Regulatorsmentioning

confidence: 99%

See 1 more Smart Citation

Treatment of Cushing's disease: a mechanistic update

Cuevas‐Ramos¹,

Fleseriu²

2014

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Lack of p27/kip1 function leads to the development of PAs (60). Furthermore, Liu et al (61) found that a selective inhibitor of CDK markedly suppressed ACTH levels and restrained growth of ACTH-secreting PAs in mice. One study revealed that germline CDKN1B mutations rendered individuals more susceptible to MEN1 (62).…”

Section: Leukemia Inhibitory Factor (Lif) Mutation and Cyclin-dependementioning

confidence: 99%

Gene mutations in Cushing's disease

Xiong

2016

Biomedical Reports

View full text Add to dashboard Cite

Abstract. Cushing's disease (CD) is a severe (and potentially fatal) disease caused by adrenocorticotropic hormone (ACTH)-secreting adenomas of the pituitary gland (often termed pituitary adenomas). The majority of ACTH-secreting corticotroph tumors are sporadic and CD rarely appears as a familial disorder, thus, the genetic mechanisms underlying CD are poorly understood. Studies have reported that various mutated genes are associated with CD, such as those in menin 1, aryl hydrocarbon receptor-interacting protein and the nuclear receptor subfamily 3 group C member 1. Recently it was identified that ubiquitin-specific protease 8 mutations contribute to CD, which was significant towards elucidating the genetic mechanisms of CD. The present study reviews the associated gene mutations in CD patients.

show abstract

“…A single zebrafish model for pituitary corticotroph adenoma has been described. 67 In this model, overexpression of the pituitary tumor transforming gene (pttg/securin) in cells of the adenohypophyseal proopiomelanocortin (POMC) lineage leads to formation of pituitary corticotroph adenomas in adult transgenic zebrafish. 67 Interestingly, adult transgenic zebrafish developed multiple signs of endocrine dysfunction, including hypercortisolemia, hyperplasia of renal steroidogenic cells, relative insulin resistance, hepatic lipidosis, and cardiomyopathy.…”

Section: Models Of Neural and Neuroendocrine Neoplasiamentioning

confidence: 99%

Zebrafish Models for Human Cancer

Shive

2012

Vet Pathol

View full text Add to dashboard Cite

For decades, the advancement of cancer research has relied on in vivo models for examining key processes in cancer pathogenesis, including neoplastic transformation, progression, and response to therapy. These studies, which have traditionally relied on rodent models, have engendered a vast body of scientific literature. Recently, experimental cancer researchers have embraced many new and alternative model systems, including the zebrafish (Danio rerio). The general benefits of the zebrafish model for laboratory investigation, such as cost, size, fecundity, and generation time, were quickly superseded by the discovery that zebrafish are amenable to a wide range of investigative techniques, many of which are difficult or impossible to perform in mammalian models. These advantages, coupled with the finding that many aspects of carcinogenesis are conserved in zebrafish as compared with humans, have firmly established a unique niche for the zebrafish model in comparative cancer research. This article introduces methods for generating cancer models in zebrafish and reviews a range of models that have been developed for specific cancer types. Keywords animal disease models, cancer, genetic modification, zebrafishThe zebrafish (Danio rerio) emerged as a model for scientific research in the 1930s, with many early studies devoted to the investigation of developmental processes in embryos. 53 The use of zebrafish in research has subsequently expanded into a broad range of disciplines. As a research species, zebrafish offer certain advantages over traditional vertebrate models, including rapid generation time, high fecundity, external embryonic development, a capacity for high stocking density in relatively small areas, and lower maintenance costs. 64 In recent years, the zebrafish has come into its own as a relevant comparative model for a diverse spectrum of human diseases.Although zebrafish are relative newcomers to the field of comparative cancer research, these small animals have emerged as a powerful tool for investigators. As vertebrate organisms, they share many features of embryonic development and adult anatomy that are critical for comparative animal models. 64,71 In the world of cancer research, this has important implications ranging from conserved signaling pathways and transcriptional regulatory mechanisms, to organogenesis and tissue differentiation, to cellular transformation and tumor initiation. Zebrafish cancer models have been produced by a variety of methods, leading to a broad spectrum of cancer susceptibilities in animals of multiple age groups. Flexibility in genetic manipulation, adaptability to current tools for cancer analysis, and capacity to define cellular and molecular interactions in vivo provide the zebrafish with its own very unique set of advantages for the investigation of cancer biology. Mechanisms for Developing Cancer Models in ZebrafishZebrafish cancer models have been developed by a number of mechanisms (Table 1). Although initial studies relied on chemical carcinogens for t...

show abstract

Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor

Cited by 124 publications

References 43 publications

Treatment of Cushing's disease: a mechanistic update

Treatment of Cushing's disease: a mechanistic update

Gene mutations in Cushing's disease

Zebrafish Models for Human Cancer

Contact Info

Product

Resources

About