In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-10-27)
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 PV/PV 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 −/− , Akt2 −/− , and Akt3 −/− 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.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-020-75529-0
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2020
detail.hit.zdb_id:
2615211-3
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