Avaliação do padrão de metilação de regiões promotoras dos genes ESR1, ESR2 e PGR na endometriose profunda intestinal
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Data
2011-07-08
Autores
Meyer, Joana Ladeira [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A endometriose é uma doença inflamatória estrógeno-dependente que afeta de 5 a 10% das mulheres em idade reprodutiva. É caracterizada pela presença de tecido endometrial fora da cavidade uterina e está associada à dismenorreia, dor pélvica e infertilidade. Os níveis de expressão dos receptores nucleares SF1 (fator esteroidogênico 1), estrógeno e progesterona estão alterados no tecido endometriótico comparado ao endométrio normal. Estudos prévios relataram que os genes codificadores dos receptores dos hormônios esteróides ESR1 (receptor de estrógeno 1), ESR2 (receptor de estrógeno 2) e progesterona (PGR) apresentam promotores alternativos que são modulados epigeneticamente por alterações na metilação do DNA, que ocorre preferencialmente nas ilhas CpG presentes nestas regiões. Em células endometriais normais foi observada uma associação entre a presença de metilação e ausência de expressão dos genes SF1 e ESR2 (receptor de estrógeno â) enquanto a perda da metilação foi correlacionada com níveis aumentados de expressão gênica na endometriose peritoneal e ovariana. Com base nestas evidências, o presente trabalho investigou o padrão de metilação dos genes PGR (promotores A e B), ESR1 (promotores A e B) e uma região intragênica ao ESR2. O promotor B do gene PGR e a ilha CpG localizada na 5’UTR do gene ESR2 foram avaliadas em 44 amostras de endometriose profunda intestinal pela técnica de MSP (Methylation-Specific Polymerase Chain Reaction). Em sete destas, também foi possível a investigação na amostra pareada de endométrio eutópico. O padrão de metilação dos promotores A e B do gene ESR1 e o promotor A do gene PGR...
Endometriosis is an estrogen-dependent inflammatory disease which affects 5 to 10% of women of reproductive age. This disease is characterized by the presence of endometrial tissue outside the uterine cavity and is associated with dysmenorrhea, pelvic pain, and infertility. Abnormal expression levels of SF1 (steroidogenic factor 1), estrogen and progesterone nuclear receptors were detected in the endometriotic tissue compared to the normal endometrium. Previous studies have reported that genes encoding the steroid hormone receptors ESR1 (estrogen receptor 1), ESR2 (estrogen receptor 2) and progesterone (PGR) are characterized by alternative promoters epigenetically regulated by DNA methylation at CpG islands co-localized in these regions. In normal endometrial cells, it was observed an association between DNA methylation and absence of expression of the genes SF1 and ESR2 (estrogen receptor â), while loss of DNA methylation was correlated with increased expression levels of these genes in peritoneal and ovarian endometriosis. Based on these findings, this study investigated the methylation pattern of the PGR (promoters A and B), ESR1 (promoters A and B) genes and an intragenic region of the gene ESR2. The promoter B of PGR gene and the CpG island mapped at 5 'UTR of the ESR2 gene were evaluated in 44 samples of intestinal deep endometriosis by MSP (methylation-specific polymerase chain reaction). In seven cases, paired samples of eutopic endometrium from the same patients were also evaluated, the methylation patterns of the ESR1 gene (promoters A and B) and the promoter region A of the PGR gene were investigated in 37 samples of endometriosis. The MSP method is based on the DNA modification by sodium bisulfite, which converts unmethylated cytosines to uracil. Subsequently, the target region... (Complete abstract click electronic access below)
Endometriosis is an estrogen-dependent inflammatory disease which affects 5 to 10% of women of reproductive age. This disease is characterized by the presence of endometrial tissue outside the uterine cavity and is associated with dysmenorrhea, pelvic pain, and infertility. Abnormal expression levels of SF1 (steroidogenic factor 1), estrogen and progesterone nuclear receptors were detected in the endometriotic tissue compared to the normal endometrium. Previous studies have reported that genes encoding the steroid hormone receptors ESR1 (estrogen receptor 1), ESR2 (estrogen receptor 2) and progesterone (PGR) are characterized by alternative promoters epigenetically regulated by DNA methylation at CpG islands co-localized in these regions. In normal endometrial cells, it was observed an association between DNA methylation and absence of expression of the genes SF1 and ESR2 (estrogen receptor â), while loss of DNA methylation was correlated with increased expression levels of these genes in peritoneal and ovarian endometriosis. Based on these findings, this study investigated the methylation pattern of the PGR (promoters A and B), ESR1 (promoters A and B) genes and an intragenic region of the gene ESR2. The promoter B of PGR gene and the CpG island mapped at 5 'UTR of the ESR2 gene were evaluated in 44 samples of intestinal deep endometriosis by MSP (methylation-specific polymerase chain reaction). In seven cases, paired samples of eutopic endometrium from the same patients were also evaluated, the methylation patterns of the ESR1 gene (promoters A and B) and the promoter region A of the PGR gene were investigated in 37 samples of endometriosis. The MSP method is based on the DNA modification by sodium bisulfite, which converts unmethylated cytosines to uracil. Subsequently, the target region... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Endometriose, Intestinos - Doenças - Aspectos genéticos, Genetica humana, Human genetics, Intestines - Diseases - Psychosomatic aspects, Endometriosis
Como citar
MEYER, Joana Ladeira. Avaliação do padrão de metilação de regiões promotoras dos genes ESR1, ESR2 e PGR na endometriose profunda intestinal. 2011. 85 f. Dissertação (mestrado) - Universidade Estadual Paulista, Instituto de Biociências de Botucatu, 2011.