Transcriptional activation of the cyclin D1 gene (CCND1) plays a pivotal role in G 1 -phase progression, which is thereby controlled by multiple regulatory factors, including nuclear receptors (NRs). Appropriate CCND1 gene activity is essential for normal development and physiology of the mammary gland, where it is regulated by ovarian steroids through a mechanism(s) that is not fully elucidated. We report here that CCND1 promoter activation by estrogens in human breast cancer cells is mediated by recruitment of a c-Jun/c-Fos/estrogen receptor ␣ complex to the tetradecanoyl phorbol acetate-responsive element of the gene, together with Oct-1 to a site immediately adjacent. This process coincides with the release from the same DNA region of a transcriptional repressor complex including Yin-Yang 1 (YY1) and histone deacetylase 1 and is sufficient to induce the assembly of the basal transcription machinery on the promoter and to lead to initial cyclin D1 accumulation in the cell. Later on in estrogen stimulation, the cyclin D1/Cdk4 holoenzyme associates with the CCND1 promoter, where E2F and pRb can also be found, contributing to the long-lasting gene enhancement required to drive G 1 -phase completion. Interestingly, progesterone triggers similar regulatory events through its own NRs, suggesting that the gene regulation cascade described here represents a crossroad for the transcriptional control of G 1 -phase progression by different classes of NRs.Mammary gland morphogenesis and development result from the interplay of genetic and epigenetic pathways, controlled by hormones, growth factors, and other signaling molecules. Derangement of one or more of these regulatory pathways results in the abnormal growth and differentiation of mammary epithelial cells, leading to breast carcinogenesis. The ovarian hormones estrogen and progesterone promote mammary gland differentiation toward the female phenotype at the onset of puberty and control breast tropism and function throughout the reproductive life by affecting epithelial cell proliferation. Mammary gland cells are endowed with highaffinity receptors for these steroids (estrogen receptor ␣ [ER␣] and ER␤ and progesterone receptor A [PR-A] and PR-B, respectively), which belong to the nuclear receptor (NR) family of transcription factors (31

These findings showed that: 1) in subjects without diabetes and patients with well-controlled diabetes, TNF-alpha, CCR5, and CXCR3 may constitute distinctive biomarkers of P-IM; 2) poor glycemic control abolished the differences between CP and P-IM regarding the expression of these mediators; and 3) type 2 diabetes affected the expression of TNF-alpha, IL-6 and -8, CCR5, and CXCR3.

Most melanomas occur on the skin, but a small percentage of these life-threatening cancers affect other parts of the body, such as the eye and mucous membranes, including the mouth. Given that most melanomas are caused by ultraviolet radiation (UV) exposure, close attention has been paid to the impact of oxidative stress on these tumors. The possibility that key epigenetic enzymes cannot act on a DNA altered by oxidative stress has opened new perspectives. Therefore, much attention has been paid to the alteration of DNA methylation by oxidative stress. We review the current evidence about (i) the role of oxidative stress in melanoma initiation and progression; (ii) the mechanisms by which ROS influence the DNA methylation pattern of transformed melanocytes; (iii) the transformative potential of oxidative stress-induced changes in global and/or local gene methylation and expression; (iv) the employment of this epimutation as a biomarker for melanoma diagnosis, prognosis, and drug resistance evaluation; (v) the impact of this new knowledge in clinical practice for melanoma treatment.

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HDF and HDF(k) have significantly different effects on QT(c). ECG data demonstrate that the risk of arrhythmia could be lower, with a variable removal of potassium during haemodialysis. With HDF but not HDF(k), hyperpolarization of the cell membrane is detected, and this could have a destabilizing effect on different types of cardiac cell, giving rise to retrograde circuits.