論文 - 詳細
| RRC ID | 47321 |
|---|---|
| 著者 | Fukuda T, Tanaka T, Hamaguchi Y, Kawanami T, Nomiyama T, Yanase T. |
| タイトル | Augmented Growth Hormone Secretion and Stat3 Phosphorylation in an Aryl Hydrocarbon Receptor Interacting Protein (AIP)-Disrupted Somatotroph Cell Line. |
| ジャーナル | PLoS One |
| Abstract |
Aryl hydrocarbon receptor interacting protein (AIP) is thought to be a tumor suppressor gene, as indicated by a mutational analysis of pituitary somatotroph adenomas. However, the physiological significance of AIP inactivation in somatotroph cells remains unclear. Using CRISPR/Cas9, we identified a GH3 cell clone (termed GH3-FTY) in which Aip was genetically disrupted, and subsequently investigated its character with respect to growth hormone (Gh) synthesis and proliferation. Compared with GH3, GH3-FTY cells showed remarkably increased Gh production and a slight increase in cell proliferation. Gh-induced Stat3 phosphorylation is known to be a mechanism of Gh oversecretion in GH3. Interestingly, phosphorylated-Stat3 expression in GH3-FTY cells was increased more compared with GH3 cells, suggesting a stronger drive for this mechanism in GH3-FTY. The phenotypes of GH3-FTY concerning Gh overproduction, cell proliferation, and increased Stat3 phosphorylation were significantly reversed by the exogenous expression of Aip. GH3-FTY cells were less sensitive to somatostatin than GH3 cells in the suppression of cell proliferation, which might be associated with the reduced expression of somatostatin receptor type 2. GH3-FTY xenografts in BALB/c nude mice (GH3-FTY mice) formed more mitotic somatotroph tumors than GH3 xenografts (GH3 mice), as also evidenced by increased Ki67 scores. GH3-FTY mice were also much larger and had significantly higher plasma Gh levels than GH3 mice. Furthermore, GH3-FTY mice showed relative insulin resistance compared with GH3 mice. In conclusion, we established a somatotroph cell line, GH3-FTY, which possessed prominent Gh secretion and mitotic features associated with the disruption of Aip. |
| 巻・号 | 11(10) |
| ページ | e0164131 |
| 公開日 | 2016-1-1 |
| DOI | 10.1371/journal.pone.0164131 |
| PII | PONE-D-16-14238 |
| PMID | 27706259 |
| PMC | PMC5051713 |
| MeSH | Adenoma / pathology* Animals Cell Line Cell Proliferation Gene Silencing Growth Hormone / metabolism* Growth Hormone-Secreting Pituitary Adenoma / pathology* Intracellular Signaling Peptides and Proteins / genetics* Intracellular Signaling Peptides and Proteins / metabolism Mice Mice, Inbred BALB C Neoplasm Transplantation Phosphorylation Rats Rho Guanine Nucleotide Exchange Factors / metabolism* STAT3 Transcription Factor / metabolism* Somatotrophs / cytology* Somatotrophs / metabolism Somatotrophs / transplantation Up-Regulation |
| IF | 2.74 |
| 引用数 | 4 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Peer-review(Publons) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-EF-Venus (RDB05552) |