Rhythmic profile assessment of breast cancer cell lines and adipose derived stem cells after circadian entrainment
López Ruiz, Eduardo Francisco
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The circadian clock is an adaptive mechanism that organisms have developed over the years as an evolutionary feature. Given its etymology, these characteristics give the body the ability to respond to the stimuli of the day with much greater efficiency. Sunlight is the main stimulus that synchronizes this mechanism and that, from the eyes, transduces signals to the whole body. Likewise, all the cells of the body have intrinsic mechanisms that can be synchronized by other stimuli such as hormones, stress or heat. This mechanism is of vital importance and is related to crucial physiological processes such as cell regeneration and proliferation. This thesis addressed two main issues. First, the induction of the circadian rhythm was confirmed through a vitamin D stimulus in a model of adipose derived stem cells. This, by means of the quantification of the gene expression of Bmal1 in a conventional procedure of bovine serum shock and induction by vitamin D. However, the oscillations in the expression of circadian gene Per2 could not be replicated as in previous study. In turn, differences were observed in the expression pattern of the different canonical genes of pluripotency. Interestingly, after a mathematical analysis, it was found that the expression of Oct4 had a behavior in synchrony with Bmal1 after treatment by fetal bovine serum. This opens the possibility of a much more direct relationship of the state of pluripotency with the canonical mechanism of circadian rhythms. Second, the protein profile of two breast cancer cell lines (MCF-7 and MDA-MB-231) was evaluated after synchronization by fetal bovine serum. Although it has been shown that the circadian molecular mechanism is not very functional in breast cancer lines, the possibility of rhythmicity in these cell lines has been explored. It was confirmed that there are rhythmic behavior patterns in both cell lines. No protein was identified with rhythmic behavior in both cell lines. However, proteins with a constant behavior over 72 hours show a strongly differential expression pattern in both groups. These findings show that the depth of the role of circadian rhythms has not yet been fully understood. In the case of the model in stem cells, a greater role in the state of pluripotency is suggested to be studied. In the case of breast cancer lines, their characterization and possible identification as therapeutic targets.