| Full text | |
| Author(s): Show less - |
Leal, Leticia Ferro
[1, 2, 3, 4]
;
Szarek, Eva
[4]
;
Berthon, Annabel
[4]
;
Nesterova, Maria
[4]
;
Faucz, Fabio R.
[4]
;
London, Edra
[4]
;
Mercier, Christopher
[4]
;
Abu-Asab, Mones
[4]
;
Starost, Matthew F.
[5]
;
Dye, Louis
[6]
;
Bilinska, Barbara
[7]
;
Kotula-Balak, Malgorzata
[8]
;
Antonini, Sonir R.
[1]
;
Stratakis, Constantine A.
[4]
Total Authors: 14
|
| Affiliation: | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, BR-14049900 Sao Paulo - Brazil
[2] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos - Brazil
[3] Dr Paulo Prata FACISB, Barretos Sch Hlth Sci, Barretos - Brazil
[4] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD 20892 - USA
[5] NIH, Div Vet Resources, Bethesda, MD 20892 - USA
[6] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Microscopy & Imaging Core, NIH, Bethesda, MD 20892 - USA
[7] Jagiellonian Univ Krakow, Inst Zool, Dept Endocrinol, Krakow - Poland
[8] Agr Univ Krakow, Univ Ctr Vet Med, Krakow - Poland
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | Molecular and Cellular Endocrinology; v. 522, FEB 15 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
PDE8B, PRKAR1A and the Wnt/beta-catenin signaling are involved in endocrine disorders. However, how PDEB8B interacts with both Wnt and protein kinase A (PKA) signaling in vivo remains unknown. We created a novel Pde8b knockout mouse line (Pde8b(-/)(-)); Pde8b haploinsufficient (Pde8b(+/-)) mice were then crossed with mice harboring: (1) constitutive beta-catenin activation (Pde8b(+/)(-);Delta Cat) and (2) Prkar1a haploinsufficieny (Pde8b(+/-);Prkar1a(+/)(-)). Adrenals and testes from mice (3-12-mo) were evaluated in addition to plasma corticosterone, aldosterone and Dkk3 concentrations, and the examination of expression of steroidogenesis-, Wnt- and cAMP/PKA-related genes. Pde8b(-/-) male mice were infertile with down-regulation of the Wnt/beta-catenin pathway which did not change significantly in the Pde8b(+/-);Delta Cat mice. Prkarla haploinsufficiency also did not change the phenotype significantly. In vitro studies showed that PDE8B knockdown upregulated the Wnt pathway and increased proliferation in CTNNB1-mutant cells, whereas it downregulated the Wnt pathway in PRKAR1Amutant cells. These data support an overall weak, if any, role for PDE8B in adrenocortical tumorigenesis, even when co-altered with Wnt signaling or PKA upregulation; on the other hand, PDE8B appears to play a significant role in male fertility. (AU) | |
| FAPESP's process: | 13/05337-3 - The interaction between Wnt canonical pathway with PRKAR1A and PDE8B in adrenocortical tumor development and/or progression by using a transgenic mouse model |
| Grantee: | Letícia Ferro Leal |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |