Oncogene-induced senescence and its evasion in a mouse model of thyroid neoplasia

被引：10

作者：

Bellelli, Roberto ^{[1
,8
]}

Vitagliano, Donata ^{[2
]}

Federico, Giorgia ^{[1
]}

Marotta, Pina ^{[3
]}

Tamburrino, Anna ^{[1
]}

Salerno, Paolo ^{[1
]}

Paciello, Orlando ^{[4
]}

Papparella, Serenella ^{[4
]}

Knauf, Jeffrey A. ^{[5
]}

Fagin, James A. ^{[5
]}

Refetoff, Samuel ^{[6
]}

Troncone, Giancarlo ^{[7
]}

Santoro, Massimo ^{[1
]}

机构：

[1] Univ Federico II, Dipartimento Med Mol & Biotecnol Med, Ist Endocrinol & Oncol Sperimentale, CNR, Via S Pansini 5, I-80131 Naples, Italy

[2] Seconda Univ Napoli, Dipartimento Med Chirurg Internist Clin & Sperime, Via S Pansini 5, I-80131 Naples, Italy

[3] Biogem, IRGS, Via Camporeale, I-83031 Avellino, Italy

[4] Univ Federico II, Dipartimento Med Vet & Prod Anim, Via Delpino 1, Naples, Italy

[5] Mem Sloan Kettering Canc Ctr, Dept Med, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA

[6] Univ Chicago, Dept Med, Dept Pediat, Comm Genet, 5841 S Maryland Ave, Chicago, IL 60637 USA

[7] Univ Federico II, Dipartimento Sanita Pubbl, Via S Pansini 5, I-80131 Naples, Italy

[8] Francis Crick Inst, DSB Repair Metab Lab, London NW1 1AT, England

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2018年 / 460卷 / 0C期

关键词：

Thyroid cancer; RET oncogene; Oncogene-induced senescence; AKT; DNA-DAMAGE-RESPONSE; TISSUE-SPECIFIC EXPRESSION; CYCLIC-AMP; BRAF(V600E)-INDUCED SENESCENCE; PAPILLARY CARCINOMAS; GENOMIC INSTABILITY; CELL PROLIFERATION; RET/PTC1; ONCOGENE; TUMOR PROGRESSION; TRANSGENIC MICE;

D O I：

10.1016/j.mce.2017.06.023

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Here we describe a conditional doxycycline-dependent mouse model of RET/PTC3 (NCOA4-RET) oncogene-induced thyroid tumorigenesis. In these mice, after 10 days of doxycycline (dox) administration, RET/PTC3 expression induced mitogen activated protein kinase (MAPK) stimulation and a proliferative response which resulted in the formation of hyperplastic thyroid lesions. This was followed, after 2 months, by growth arrest accompanied by typical features of oncogene-induced senescence (OIS), including upregulation of p16INK4A and p21CIP, positivity at the Sudan black B, activation of the DNA damage response (DDR) markers gamma H2AX and pChk2 T68, and induction of p53 and p19ARF. After 5 months, about half of thyroid lesions escaped OIS and formed tumors that remained dependent on RET/PTO expression. This progression was accompanied by activation of AKT-FOXO1/3a pathway and increased serum TSH levels. (C) 2017 Elsevier B.V. All rights reserved.

引用

页码：24 / 35

页数：12

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