The Role of Biological Clock in Gynecologic Cancer

Abstract

Disruption in coordinated co-expression of clock genes, like Period genes mutations, is linked with the increased risk of lung, gastrointestinal, hematologic and gynecologic cancers. Several clock genes have been found to functionally interplay with regulators of the cell cycle. It is suggested that abnormal cell cycle function in cancer could also be a consequence of a disrupted biological clock. Chrono-disruption, being studied in different cancer entities, including the gynecologic cancer, could provide time set intervention in cancer therapeuticschronotherapy in a 24 h-period.

Shift and longtime light induces endometrioid adenocarcinoma via activation of PKC‐α/Akt pathway in female golden hamster: Involvement of altered Aanat and Bmal1 rhythm

“…15,16 Dysfunction in the clock alters the expressions of these clock-controlled tumor-related genes and their downstream cellular pathways, hence, contributing to carcinogenesis, activated Per2 that promotes tumor by inducing C-Myc overexpression and lowered expression of Per1 as a link with endometrial cancer, antiphase expressions of Cry1 and Bmal1 causes ovarian cancer, and so forth. 5,[17][18][19] Previously we have reported that long duration of light in circadian desynchronization leads to pregnancy anomalies of hamsters. 20 Therefore, we may suggest that both melatonin and clock genes are involved in the initiation and progression of gynecological cancers, while the Bmal1 and Aanat genes are worth targeting for the etiology of artificial light-associated endometrial cancer.…”

“…Studies have reported oncostatic properties of melatonin in mammary tumors by potential antiestrogenic and antiaromatase activities 15,16 . Dysfunction in the clock alters the expressions of these clock‐controlled tumor‐related genes and their downstream cellular pathways, hence, contributing to carcinogenesis, activated Per2 that promotes tumor by inducing C‐Myc overexpression and lowered expression of Per1 as a link with endometrial cancer, antiphase expressions of Cry1 and Bmal1 causes ovarian cancer, and so forth 5,17–19 . Previously we have reported that long duration of light in circadian desynchronization leads to pregnancy anomalies of hamsters 20 .…”

“…The chronodisrupters and the untimely artificial light exposure have hazardous effects not only in animals, but also for humans 1 . Circadian rhythms regulated by the master clock, superchiasmatic nucleus located in the hypothalamus, constitutes of core clock genes such as Bmal1, Clock, Per1‐2 and Cry1‐2 , 2 are being rhythmically coordinated with clocks of peripheral tissues 3–5 . Dysregulation of clock genes expression are associated with several disorders, such as insomnia, depression, obesity, hypertension, and cancer 6,7 .…”

“…1 Circadian rhythms regulated by the master clock, superchiasmatic nucleus located in the hypothalamus, constitutes of core clock genes such as Bmal1, Clock, Per1-2 and Cry1-2, 2 are being rhythmically coordinated with clocks of peripheral tissues. [3][4][5] Dysregulation of clock genes expression are associated with several disorders, such as insomnia, depression, obesity, hypertension, and cancer. 6,7 The most studied malignancies are various types of cancer such as lung, prostate, and breast cancer.…”