Circadian Rhythms and Breast Cancer: The Role of Per2 in Doxorubicin-Induced Cell Death

Journal of Toxicology
Megan I Mitchell, Anna-Mart Engelbrecht

Abstract

Mammalian circadian rhythms form an integral physiological system allowing for the synchronisation of all metabolic processes to daily light/dark cycles, thereby optimising their efficacy. Circadian disruptions have been implicated in the onset and progression of various cancers, including those arising in the breast. Several links between the circadian protein Per2 and DNA damage responses exist. Aberrant Per2 expression results in potent downstream effects on both cell cycle and apoptotic targets, suggestive of a tumour suppressive role for Per2. Due to the severe dose limiting side effects associated with current chemotherapeutic strategies, including the use of doxorubicin, a need for more effective adjuvant therapies to increase cancer cell susceptibility has arisen. This study was therefore aimed at characterizing the role of Per2 in normal breast epithelia (MCF-12A) and in ER(-) breast cancer cells (MDA-MB-231) and also at determining the role of Per2 in doxorubicin-induced cell death. In both cell lines Per2 protein expression displayed a 24-hour circadian rhythm in both cell lines. Per2 was located predominantly in the cytoplasm, with nuclear localization observed with lower cytoplasmic fluorescent intensities. Our res...Continue Reading

References

Jan 18, 1989·Journal of the National Cancer Institute·R B SothernW J Hrushesky
Apr 5, 1985·Science·W J Hrushesky
Feb 23, 1999·The American Journal of Pathology·G A BjarnasonR B Sothern
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Jan 11, 2002·Molecular and Cellular Biology·Claudia CrosioPaolo Sassone-Corsi
May 2, 2002·Journal of the National Cancer Institute·Elisabeth FilipskiFrancis Lévi
Feb 11, 2003·Nature Cell Biology·Ming-Ying TsaiYixian Zheng
Aug 23, 2003·Science·Takuya MatsuoHitoshi Okamura
Nov 17, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Teresa G GrandaFrancis Lévi
Mar 16, 2005·Molecular and Cellular Biology·Erik J EideDavid M Virshup
Mar 26, 2005·Carcinogenesis·Shou-Tung ChenJan-Gowth Chang
Apr 6, 2006·Cancer Causes & Control : CCC·Elizabeth FilipskiFrancis Lévi
Mar 13, 2008·Journal of Circadian Rhythms·Shulin XiangSteven M Hill
Apr 24, 2008·BMC Molecular Biology·Sonja LangmesserUrs Albrecht
Apr 26, 2008·Autophagy·Uma M Sachdeva, Craig B Thompson
Dec 1, 2007·The Lancet Oncology·Kurt StraifUNKNOWN WHO International Agency For Research on Cancer Monograph Working Group
Nov 21, 2009·Integrative Cancer Therapies·Xiaoming YangWilliam J M Hrushesky
Aug 6, 2013·Current Biology : CB·Kenneth P WrightEvan D Chinoy
Aug 21, 2013·Trends in Cell Biology·Kaleigh Fernald, Manabu Kurokawa
Oct 9, 2013·Cancer Letters·Fergal C KelleherAnne Maguire
Nov 28, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Zhao-lei ZengRui-hua Xu

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Citations

Oct 31, 2018·Scientific Reports·Tuba KorkmazNuri Ozturk
Dec 7, 2018·Frontiers in Genetics·Yaroslav R EfremovSergey S Bogachev
Oct 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sadia RahmanElitza P Markova-Car

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Methods Mentioned

BETA
transfection
electrophoresis
flow cytometry

Software Mentioned

Quantity One
GraphPad Prism
KCjunior
ModFit LT
ImageLab

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