Advanced search
Start date

To investigate the role of TP53 in adrenocortical zonation through targeted disruption in Aldosterone Synthase (AS)-expressing adrenal cells during post-natal development, maintenance and regeneration

Grant number: 16/00862-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): September 01, 2016
Effective date (End): August 31, 2017
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal researcher:Carlos Alberto Scrideli
Grantee:Kleiton Silva Borges
Supervisor abroad: David Breault
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: Harvard University, Boston, United States  
Associated to the scholarship:13/23419-7 - Functional study of the TP53 p.R337H mutation in cell lines grown under alkaline conditions, BP.PD


The human adult adrenal cortex is composed of the zona glomerulosa (zG), zona fasciculata (zF), and zona reticularis (zR), which are responsible for production of mineralocorticoids, glucocorticoids, and adrenal androgens, respectively. Starting shortly after birth, a rapid, dramatic remodeling of adrenal cortex structure takes place, with massive shrinkage of the gland due to apoptosis of the fetal zone and progressive differentiation of the definitive adrenocortical zones, which are the hallmark of the adult adrenal. Recently, through cell fate mapping and gene deletion studies using zG-specific Cre expression, Dr. Breault's team demonstrated that differentiated zG cells undergo lineage conversion into zF cells and that zG-specific Sf-1 deletion prevents such lineage conversion. These findings lead us to hypothesize that other genes may also be regulating this process. TP53 gene is a transcription factor and an important tumour suppressor that is inactivated in most cancers. The high incidence of pediatric adrenocortical tumors in children with germline TP53 mutations suggests that normal p53 function is required for the physiological process of postnatal fetal adrenal. Interestingly, TP53 mutation is not by itself sufficient to promote adrenocortical tumorigenesis but must cooperate with other genetic alterations, such as activation of Wnt/²-catenin. Wnt/²-catenin signaling is critical for adrenal homeostasis and the crosstalk between p53 and Wnt signaling pathways has been showed by previous studies. However, it has never been investigated in the context of adrenocortical zonation. Here, we hypothesize that targeted disruption of p53 in Aldosterone Synthase (AS)-expressing cells (zG specific) may lead to aberrant B-catenin activity affecting adrenocortical homeostasis, zonation, regenerative capacity and tumor susceptibility. To test this hypothesis, we will explore the role of p53 in mouse adrenocortical zonation through its targeted disruption in Aldosterone Synthase (AS)-expressing adrenal cells during post-natal development, tissue maintenance and regeneration. This approach could provide essential new insight into adrenal development and tumor formation.

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BORGES, KLEITON SILVA; PIGNATTI, EMANUELE; LENG, SINING; KARIYAWASAM, DULANJALEE; RUIZ-BABOT, GERARD; RAMALHO, FERNANDO SILVA; TAKETO, MAKOTO MARK; CARLONE, DIANA L.; BREAULT, DAVID T.. Wnt/beta-catenin activation cooperates with loss of p53 to cause adrenocortical carcinoma in mice. Oncogene, v. 39, n. 30, . (16/00862-0)

Please report errors in scientific publications list by writing to: