Circadian Clock and Breast Cancer: A Molecular Link

Abstract

The circadian clock controls a large array of behavioral and physiological systems of fundamental importance to most organisms. Consequently, abnormal functioning of the clock results in severe dysfunctions and pathologies. Although epidemiological studies show a clear correlation between disruption of circadian rhythms and incidence of breast cancer, a molecular interpretation of how clock-related mechanisms may link to tumor development remains elusive. Here we speculate on the molecular pathways that may couple the circadian machinery to breast cancer.

Night‐time work predisposes to non‐Hodgkin lymphoma

“…20 Moreover, the efficacy of chemotherapies appears to be better at particular time of the day 21 and the prognosis of cancer poorer in those patients having disrupted circadian rhythms. 22 These observations give support to the assumption that there is a circadian effect on cancer. Subsequently, abnormalities in the circadian clockwork due to night-time work may predispose to cancers whose progression is influenced by the circadian effect.…”

Regulation of Mammary Development as It Relates to Changes in Milk Production Efficiency

“…For over 30 years, melatonin has had an implicated role in mammary development due to its association with the incidence of breast cancer (Cohen et al, 1978). Indeed, a direct negative relationship between melatonin treatment or presence of the pineal gland and the development of mammary cancer was reported long ago (Tamarkin et al, 1981), and it has subsequently been well documented that melatonin inhibits mammary cancer (For reviews see Cos & Sanchez-Barcelo, 2000;Sanchez-Barcelo et al, 2003;Sahar & Sassone-Corsi, 2007;Pandi-Perumal et al, 2008). Because melatonin is secreted during the dark, and has a negative effect on breast cancer risk, the incidence of breast cancer is increased in night-shift workers and people with sleep disturbances (Stevens, 2006;Blask, 2009), and decreased in the blind (Feychting et al, 1998).…”

Entrainment of breast (cancer) epithelial cells detects distinct circadian oscillation patterns for clock and hormone receptor genes

“…Disruption of endogenous circadian rhythms seem to have a major impact on overall health and has been correlated with aging and diseases, such as coronary heart disease, various neurodegenerative disorders and cancer. [1][2][3][4][5][6][7][8][9] The generation of endogenous circadian rhythms is now known to be an attribute of each individual cell's own molecular time piece, hereafter referred to as circadian oscillator or clock. This clock is based on a genetic network of transcriptional and post-translational negative feedback loops that generate rhythmic 24 h expression of core clock components.…”