A Toxicogenomic Approach Reveals a Novel Gene Regulatory Network Active in In Vitro and In Vivo Models of Thyroid Carcinogenesis

Carla Reale, Filomena Russo, Sara Carmela Credendino, Danila Cuomo, Gabriella De Vita, Massimo Mallardo, Francesca Pennino, Immacolata Porreca, Maria Triassi, Mario De Felice and Concetta Ambrosino
Additional contact information
Carla Reale: IRGS, Biogem, Via Camporeale, 83031 Ariano Irpino, Avellino, Italy
Filomena Russo: IRGS, Biogem, Via Camporeale, 83031 Ariano Irpino, Avellino, Italy
Sara Carmela Credendino: Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy
Danila Cuomo: Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843, USA
Gabriella De Vita: Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy
Massimo Mallardo: Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy
Francesca Pennino: Department of Public Health, University of Naples “Federico II”, 80131 Naples, Italy
Immacolata Porreca: Human Genetics, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
Maria Triassi: Department of Public Health, University of Naples “Federico II”, 80131 Naples, Italy
Mario De Felice: Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy
Concetta Ambrosino: IRGS, Biogem, Via Camporeale, 83031 Ariano Irpino, Avellino, Italy

IJERPH, 2019, vol. 16, issue 1, 1-17

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.

Keywords: pesticides; TCDD; gene expression; thyroid cancer; cell survival (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

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