RESUMO
Estrogens play a key role in breast cancer, with 60-70% of the cases expressing estrogen receptors (ERs), which are encoded by the ESR1 gene. CTCFL, a paralogue of the chromatin organizer CTCF, is a potential biomarker of breast cancer, but its expression in this disease is currently controversial. A positive correlation has been reported between CTCFL and ERs in breast tumors and there also exists a coordinated interaction between CTCF and ERs in breast cancer cells. Therefore, there appears to be an association between CTCF, CTCFL and estrogens in breast cancer; however, there has been no report on the effects of estrogens on CTCF and CTCFL expression. The aim of this study was to determine the effect of 17ß-estradiol (E2) on the CTCF and CTCFL mRNA expression in the MCF7 breast cancer cell line. The promoter methylation status of CTCFL and data mining for estrogen response elements in promoters of the CTCF and CTCFL genes were also determined. The transcription of CTCF and CTCFL was performed by quantitative polymerase chain reaction (qPCR) and the promoter methylation status of CTCFL was determined by methylation-specific PCR. The MCF7 cells exhibited basal transcription of CTCF, which was significantly downregulated to 0.68 by 1 µM E2; basal or E2-regulated transcription of CTCFL was not detected. Under basal conditions, the CTCFL promoter was methylated. Through data mining, an estrogen response element was identified in the CTCF promoter, but no such element was found in CTCFL. These results suggested that estrogens may modulate CTCF expression, although there was no apparent association between ERs and CTCFL.
RESUMO
BACKGROUND AND OBJECTIVE: Cognitive impairment and dementia are common geriatric syndromes in diabetic patients. Inflammation plays a crucial role in the pathophysiology of Alzheimer's disease and cognitive impairment. Cyclooxygenases (COX) 1 and 2 participate in inflammation. The polymorphism c.1-765G>C of the COX2 gene might be protective against cognitive decline in Mexicans with diabetes mellitus through its reduced promotor activity. To determine the association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in elderly adults with diabetes. PATIENTS AND METHODS: Case-control study. We included diabetic patients from the Geriatric Clinic of General Hospital No. 17 who were over 65 years and accepted to participate. Cases were patients with a score of 24 or less on the Mini Mental Status Examination (MMSE) and with DSM IV criteria for dementia. Controls were those with MMSE scores of 25 or greater. Results We included 97 patients (50 cases and 47 controls). There were no differences regarding clinical and laboratory characteristics between cases and controls. The frequency of the C allele and the CG genotype was higher in controls than in cases and this difference remained significant in a multivariate analysis with an odds ratio of 0.012 (95% CI 0.001-0.091) and 0.009 (95% CI 0.001-0.076) in the bivariate and multivariate analysis, respectively, using the GG genotype frequency as a reference. CONCLUSION: Cognitive impairment in Mexican patients with diabetes is associated with less exposure to the CG genotype of the c.1-765G>C polymorphism of COX2.