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Akt isoform-specific effects on thyroid cancer development and progression in a murine thyroid cancer model.
- Source :
-
Scientific reports [Sci Rep] 2020 Oct 27; Vol. 10 (1), pp. 18316. Date of Electronic Publication: 2020 Oct 27. - Publication Year :
- 2020
-
Abstract
- The Akt family is comprised of three unique homologous proteins with isoform-specific effects, but isoform-specific in vivo data are limited in follicular thyroid cancer (FTC), a PI3 kinase-driven tumor. Prior studies demonstrated that PI3K/Akt signaling is important in thyroid hormone receptor β <superscript>PV/PV</superscript> knock-in (PV) mice that develop metastatic thyroid cancer that most closely resembles FTC. To determine the roles of Akt isoforms in this model we crossed Akt1 <superscript>-/-</superscript> , Akt2 <superscript>-/-</superscript> , and Akt3 <superscript>-/-</superscript> mice with PV mice. Over 12 months, thyroid size was reduced for the Akt null crosses (p < 0.001). Thyroid cancer development and local invasion were delayed in only the PVPV-Akt1 knock out (KO) mice in association with increased apoptosis with no change in proliferation. Primary-cultured PVPV-Akt1KO thyrocytes uniquely displayed a reduced cell motility. In contrast, loss of any Akt isoform reduced lung metastasis while vascular invasion was reduced with Akt1 or 3 loss. Microarray of thyroid RNA displayed incomplete overlap between the Akt KO models. The most upregulated gene was the dendritic cell (DC) marker CD209a only in PVPV-Akt1KO thyroids. Immunohistochemistry demonstrated an increase in CD209a-expressing cells in the PVPV-Akt1KO thyroids. In summary, Akt isoforms exhibit common and differential functions that regulate local and metastatic progression in this model of thyroid cancer.
- Subjects :
- Animals
Disease Models, Animal
Disease Progression
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic
Mice
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Protein Isoforms
Receptors, Thyroid Hormone metabolism
Thyroid Gland metabolism
Thyroid Neoplasms metabolism
Thyroid Neoplasms pathology
Proto-Oncogene Proteins c-akt metabolism
Thyroid Neoplasms etiology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33110146
- Full Text :
- https://doi.org/10.1038/s41598-020-75529-0