| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2019-03-07 |
| タイトル |
|
|
タイトル |
Inhibitory effects of a selective Jak2 inhibitor on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT20 cells |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 著者 |
Asari, Yuko
Kageyama, Kazunori
Nakada, Yuki
Tasso, Mizuki
Takayasu, Shinobu
Niioka, Kanako
Ishigame, Noriko
Daimon, Makoto
|
| 著者所属 |
|
|
|
Hirosaki Univ, Grad Sch Med, Dept Endocrinol & Metab |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Purpose: The primary cause of Cushing's disease is adrenocorticotropic hormone ( ACTH)producing pituitary adenomas. EGFR signaling induces POMC mRNA-transcript levels and ACTH secretion from corticotroph tumors. The Jak-STAT pathway is located downstream of EGFR signaling; therefore, a Jak2 inhibitor could be an effective therapy for EGFR-related tumors. In this study, we determined the effect of a potent and selective Jak2 inhibitor, SD1029, on ACTH production and proliferation in mouse AtT20 corticotroph tumor cells.
Materials and methods: AtT20 pituitary corticotroph tumor cells were cultured after transfection with PTTG1- or GADD45 beta-specific siRNA. Expression levels of mouse POMC, PTTG1, and GADD45 beta mRNAs were evaluated using quantitative real-time polymerase chain reaction. ACTH levels were measured using ACTH ELISA. Western blot analysis was performed to examine protein expression of phosphorylated STAT3/STAT3. Viable cells and DNA fragmentation were measured using a cell-proliferation assay and cell-death detection ELISA, respectively. Cellular DNA content was analyzed using fluorescence-activated cell sorting.
Results: SD1029 decreased POMC and PTTG1 mRNA and ACTH levels, while increasing GADD45 beta levels. The drug also decreased AtT20-cell proliferation and induced apoptosis, but did not alter cell-cycle progression. SD1029 also inhibited STAT3 phosphorylation. PTTG1 knockdown inhibited POMC mRNA levels and cell proliferation. However, combined treatment with PTTG1 knockdown and SD1029 had no additive effect on POMC mRNA levels or cell proliferation. GADD45 beta knockdown inhibited the SD1029-induced decrease in POMC mRNA levels and also partially inhibited the decrease in cell proliferation.
Conclusion: Both PTTG1 and GADD45 beta may be responsible, at least in part, for the Jak2-induced suppression of ACTH synthesis and cell proliferation. Accordingly, therapies that target EGFR-dependent Jak2/STAT3 may have clinical applications for treating Cushing's disease. |
| 書誌情報 |
ONCOTARGETS AND THERAPY
巻 10,
p. 4329-4338,
発行日 2017
|
| ISSN |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1178-6930 |
| DOI |
|
|
関連タイプ |
isIdenticalTo |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.2147/OTT.S141345 |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 資源タイプ |
|
|
値 |
Article |
OTT-141345-inhibitory-effects-of-a-selective-jak2-inhibitor-on-adrenoco_090117 (702.8 kB)
