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Oncogene-induced senescence and its evasion in a mouse model of thyroid neoplasia
- Source :
- Molecular and cellular endocrinology. 460
- Publication Year :
- 2015
-
Abstract
- 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 γH2AX 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/ PTC3 expression. This progression was accompanied by activation of AKT-FOXO1/3a pathway and increased serum TSH levels.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Male
endocrine system diseases
Thyroid Gland
Thyrotropin
Apoptosis
medicine.disease_cause
Biochemistry
Endocrinology
Phosphorylation
Thyroid cancer
Cellular Senescence
Thyroid
Forkhead Transcription Factors
medicine.anatomical_structure
RET oncogene
Female
Senescence
medicine.medical_specialty
endocrine system
DNA damage
Mice, Transgenic
Biology
Article
03 medical and health sciences
Downregulation and upregulation
Internal medicine
medicine
Animals
Thyroid Neoplasms
Protein kinase B
Molecular Biology
Hyperplasia
AKT
Oncogene-induced senescence
Oncogenes
medicine.disease
Enzyme Activation
Disease Models, Animal
Thyroxine
030104 developmental biology
Thyroid Epithelial Cells
Cancer research
Cattle
Carcinogenesis
Proto-Oncogene Proteins c-akt
DNA Damage
Subjects
Details
- ISSN :
- 18728057
- Volume :
- 460
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular endocrinology
- Accession number :
- edsair.doi.dedup.....009472868834c4b103a5a096a391ba18