Genetic models of Cushing’s disease: From cells, in vivo transgenic models to human pituitary organoids

被引：0
作者：
Hiba Hashmi [1 ]
Ryusaku Matsumoto [2 ]
Dylan Corcoran [3 ]
Yasuhiko Kawakami [4 ]
Takako Araki [4 ]
机构：
[1] Division of Endocrinology & Metabolism, Department of Medicine, Western University, London, ON
[2] Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Minnesota, 420 Delaware SE, Minneapolis, MN
[3] Center for Ips Cell Research and Application, Kyoto University, Kyoto
[4] Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN
[5] Stem Cell Institute, University of Minnesota, Minneapolis, MN
来源：
Pituitary | 2025年 / 28卷 / 2期
关键词：
Corticotroph tumors; Cushing disease; Genetic models; IPS cells; Pituitary organoids;
D O I：
10.1007/s11102-025-01516-1
中图分类号：
学科分类号：
摘要：
Cushing’s disease (CD) is caused by pituitary tumors that overproduce adrenocorticotropic hormone (ACTH); however, effective medical treatments remain limited, significantly impairing patients’ quality of life and prognosis. Despite extensive molecular analyses, the pathogenesis of CD remains unclear. Although previous molecular studies have relied heavily on rodent-derived cells and rodent transgenic models, significant species differences exist in the tumorigenesis of CD between humans and rodents. To date, an established human CD cell model is lacking, as human CD cells are limited in availability and sustainability over time. Additionally, the gene modifications used in transgenic models do not necessarily reflect the causative genes in CD. CD tumors exhibit wide phenotypic heterogeneity, which further complicates the development of an ideal genetic model. In this review, we provide an analysis of 11 genetic models used to study CD, outlining their historical development, strengths, and limitations. Additionally, we discuss the ongoing development of human induced pluripotent stem cell (iPSC)-derived pituitary organoids and further describe various models of pituitary organoids as an emerging novel approach to studying CD. By comparing all these models, we highlight the necessity of advancing genetic models to improve our understanding and treatment of CD. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
引用
收藏
相关论文
共 76 条
[41]  
Murphy D., Bishop A., Rindi G., Murphy M.N., Stamp G.W., Hanson J., Polak J.M., Hogan B., Mice transgenic for a vasopressin-SV40 hybrid oncogene develop tumors of the endocrine pancreas and the anterior pituitary. A possible model for human multiple endocrine neoplasia type 1, Am J Pathol, 129, pp. 552-566, (1987)
[42]  
Lee A.K., Tse F.W., Tse A., Arginine vasopressin potentiates the stimulatory action of CRH on pituitary corticotropes via a protein kinase C-dependent reduction of the background TREK-1 current, Endocrinology, 156, 10, pp. 3661-3672, (2015)
[43]  
Low M.J., Liu B., Hammer G.D., Rubinstein M., Allen R.G., Post-translational processing of proopiomelanocortin (POMC) in mouse pituitary melanotroph tumors induced by a POMC-simian virus 40 large T antigen transgene, J Biol Chem, 268, 33, pp. 24967-24975, (1993)
[44]  
Sherr C.J., McCormick F., The RB and p53 pathways in cancer, Cancer Cell, 2, 2, pp. 103-112, (2002)
[45]  
Fletcher O., Easton D., Anderson K., Gilham C., Jay M., Peto J., Lifetime risks of common cancers among retinoblastoma survivors, J Natl Cancer Inst, 96, 5, pp. 357-363, (2004)
[46]  
Jacks T., Fazeli A., Schmitt E.M., Bronson R.T., Goodell M.A., Weinberg R.A., Effects of an Rb mutation in the mouse, Nature, 359, 6393, pp. 295-300, (1992)
[47]  
Harrison D.J., Hooper M.L., Armstrong J.F., Clarke A.R., Effects of heterozygosity for the Rb-1t19neo allele in the mouse, Oncogene, 10, 8, pp. 1615-1620, (1995)
[48]  
Hu Q.J., Lees J.A., Buchkovich K.J., Harlow E., The retinoblastoma protein physically associates with the human cdc2 kinase, Mol Cell Biol, 12, 3, pp. 971-980, (1992)
[49]  
Cryns V.L., Alexander J.M., Klibanski A., Arnold A., The retinoblastoma gene in human pituitary tumors, J Clin Endocrinol Metab, 77, 3, pp. 644-646, (1993)
[50]  
Tobia C., De Sena G., Presta M., Zebrafish embryo, a tool to study tumor angiogenesis, Int J Dev Biol, 55, 4-5, pp. 505-509, (2011)
12345678