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A Toxicogenomic Approach Reveals a Novel Gene Regulatory Network Active in In Vitro and In Vivo Models of Thyroid Carcinogenesis
- Source :
- International Journal of Environmental Research and Public Health, Vol 16, Iss 1, p 122 (2019), International Journal of Environmental Research and Public Health, Volume 16, Issue 1, International journal of environmental research and public health (Online) 16 (2019). doi:10.3390/ijerph16010122, info:cnr-pdr/source/autori:Reale C.; Russo F.; Credendino S.C.; Cuomo D.; De Vita G.; Mallardo M.; Pennino F.; Porreca I.; Triassi M.; De Felice M.; Ambrosino C./titolo:A toxicogenomic approach reveals a novel gene regulatory network active in in vitro and in vivo models of thyroid carcinogenesis/doi:10.3390%2Fijerph16010122/rivista:International journal of environmental research and public health (Online)/anno:2019/pagina_da:/pagina_a:/intervallo_pagine:/volume:16
- Publication Year :
- 2019
-
Abstract
- Epidemiological and experimental studies emphasize the link between environmental chemicals exposure and thyroid cancer. However, this association is strongly debated and the mechanisms of action of environmental thyroid carcinogens still need to be identified. The analysis of in vitro transcriptomic data developed to investigate the effects of chlorpyrifos on immortalized thyrocytes highlighted the impaired expression of genes involved in endodermal carcinogenesis. This endodermal carcinogenic gene-network (ECGN, including Zfp36l2, Dmbt1, Ddit4), was validated in cellular and mouse models of thyroid carcinogenesis, characterized by the constitutive activation of the mitogen-activated protein kinase (MAPK) pathway and in immortalized thyrocytes exposed to tetrachlorodibenzo-p-dioxin (TCDD) and chlorpyrifos (CPF). The mRNA levels of Zfp36l2, Dmbt1 and Ddit4 were increased in models characterized by MAPK activation or following TCDD exposure, whereas they were inhibited by CPF exposure. Overall, the ECGN transcripts identify a novel gene-regulatory network associated with thyroid carcinogenesis promoted by genetic mutation or by environmental carcinogens. The latter have opposite effects on the modulation of the ECGN transcripts according to their mechanisms of action in promoting carcinogenesis. Therefore, the analyses of ECGN might be helpful in discriminating compounds that promote cellular survival associated or not to proliferation of thyrocytes.
- Subjects :
- MAPK/ERK pathway
TCDD
Polychlorinated Dibenzodioxins
Carcinogenesis
Health, Toxicology and Mutagenesis
lcsh:Medicine
medicine.disease_cause
Transcriptome
cell survival
gene expression
pesticides
thyroid cancer
Mice
0302 clinical medicine
Pregnancy
Gene Regulatory Networks
Maternal-Fetal Exchange
Thyroid cancer
0303 health sciences
DDIT4
biology
Thyroid
3. Good health
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
Chlorpyrifos
Mitogen-Activated Protein Kinases
Receptors, Cell Surface
Article
Cell Line
03 medical and health sciences
Tristetraprolin
medicine
Animals
Thyroid Neoplasms
Protein kinase A
Carcinogen
pesticide
030304 developmental biology
lcsh:R
Public Health, Environmental and Occupational Health
medicine.disease
Rats
Thyroid Epithelial Cells
Carcinogens
Cancer research
biology.protein
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- International Journal of Environmental Research and Public Health, Vol 16, Iss 1, p 122 (2019), International Journal of Environmental Research and Public Health, Volume 16, Issue 1, International journal of environmental research and public health (Online) 16 (2019). doi:10.3390/ijerph16010122, info:cnr-pdr/source/autori:Reale C.; Russo F.; Credendino S.C.; Cuomo D.; De Vita G.; Mallardo M.; Pennino F.; Porreca I.; Triassi M.; De Felice M.; Ambrosino C./titolo:A toxicogenomic approach reveals a novel gene regulatory network active in in vitro and in vivo models of thyroid carcinogenesis/doi:10.3390%2Fijerph16010122/rivista:International journal of environmental research and public health (Online)/anno:2019/pagina_da:/pagina_a:/intervallo_pagine:/volume:16
- Accession number :
- edsair.doi.dedup.....f0691876b168531ee10a42f3dcd60860