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Clock genes and cancer development in particular in endocrine tissues

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Angelousi, Anna, Kassi, Eva, Ansari-Nasiri, Narjes, Randeva, Harpal, Kaltsas, Gregory and Chrousos, George (2019) Clock genes and cancer development in particular in endocrine tissues. Endocrine-Related Cancer, 26 (6). R305-R317. doi:10.1530/ERC-19-0094 ISSN 1351-0088.

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Official URL: http://dx.doi.org/10.1530/ERC-19-0094

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Abstract

Circadian rhythms at a central and peripheral level are operated by transcriptional/ translational feedback loops involving a set of genes called ‘clock genes’ that have been implicated in the development of several diseases, including malignancies. Dysregulation of the Clock system can influence cancer susceptibility by regulating DNA damage and repair mechanisms, as well as apoptosis. A number of oncogenic pathways can be dysregulated via clock genes’ epigenetic alterations, including hypermethylation of clock genes’ promoters or variants of clock genes. Clock gene disruption has been studied in breast, lung and prostate cancer, and haematological malignancies. However, it is still not entirely clear whether clock gene disruption is the cause or the consequence of tumourigenesis and data in endocrine neoplasms are scarce. Recent findings suggest that clock genes are implicated in benign and malignant adrenocortical neoplasias. They have been also associated with follicular and papillary thyroid carcinomas and parathyroid adenomas, as well as pituitary adenomas and craniopharyngiomas. Dysregulation of clock genes is also encountered in ovarian and testicular tumours and may also be related with their susceptibility to chemotherapeutic agents. The most common clock genes that are implicated in endocrine neoplasms are PER1, CRY1; in most cases their expression is downregulated in tumoural compared to normal tissues. Although there is still a lot to be done for the better understanding of the role of clock genes in endocrine tumourigenenesis, existing evidence could guide research and help identify novel therapeutic targets aiming mainly at the peripheral components of the clock gene system.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: Endocrine-Related Cancer
Publisher: BioScientifica
ISSN: 1351-0088
Official Date: June 2019
Dates:
DateEvent
June 2019Published
4 April 2019Accepted
Volume: 26
Number: 6
Page Range: R305-R317
DOI: 10.1530/ERC-19-0094
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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