Browsing by Author "Tsai, Eing-Mei"

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Breast cancer is associated with methylation and expression of the a disintegrin and metalloproteinase domain 33 (ADAM33) gene affected by endocrine-disrupting chemicals
(2018-11-01)
Yang, Pei-Jing
;
Hou, Ming-Feng
;
Tsai, Eing-Mei
;
Liang, Shih-Shin
;
Chiu, Chien-Chih
A disintegrin and metalloproteinase domain 33 (ADAM33) gene is a transmembrane glycoprotein that mediates changes in cell adhesion and plays an important role in cancer progression. Since bisphenol A (BPA) and phthalates are epigenetically toxic, the purpose of this study was to examine whether BPA and phthalate metabolites, including monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MIBP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), have an epigenetic impact on ADAM33 and the incidence of breast cancer. CpG islands of breast cancer microarray data-sets obtained from the Gene Expression Omnibus (GEO) were used to assess the ADAM33 methylation profile. We designed a case-control study including 44 cases and 22 age-matched controls to detect the methylation status of intron 1 in ADAM33 from peripheral blood mononuclear cells (PBMCs) in blood, using BSP, nested PCR, and bisulfite sequencing, and measured the in vivo gene expression of ADAM33 and the urinary concentrations of endocrine-disrupting chemicals (EDCs), using real-time PCR, high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Only one dataset, GSE32393, reached significance (P=0.016). ADAM33 expression and methylation frequencies at CpG site 3 in intron 1 were higher in the control group. We found a positive association between intron 1 methylation level and ADAM33 expression as well as urinary concentrations of MEHHP, MECPP, MEOHP and Sigma 4MEHP (the sum of MEHP, MECPP, MEHHP, and MEOHP) in the cases. This study suggests that metabolites of phthalate such as MEHHP, MECPP, MEOHP and Sigma 4MEHP may increase the intron 1 methylation level to elevate ADAM33 gene expression and have a protective effect on reducing the risk of breast cancer.
Killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen-C (HLA-C) allorecognition patterns in women with endometriosis
(2020-03-17)
Chou, Ya-Ching
;
Chen, Chi-Huang
;
Chen, Ming-Jer
;
Chang, Ching-Wen
;
Chen, Pi-Hua
Endometriosis shares similarities with several autoimmune diseases. The human leukocyte antigen (HLA)-C genotype is associated with several human autoimmune diseases. HLA-C is a ligand of killer cell immunoglobulin receptors (KIRs) and is an essential regulator of natural killer cell activity, which is associated with endometriosis progression. Polymorphisms in HLA-C and KIR affect the activity of NK cells and susceptibility to several diseases. Therefore, we attempted to investigate an association between HLA-C genotype and KIR polymorphism and the occurrence of endometriosis. We tested the association of certain KIR and HLA-C combinations and the development of endometriosis by characterizing both KIR and HLA-C genes in 147 women with endometriosis and 117 controls. The HLA-C genotypes and KIR polymorphisms were analyzed via DNA-based method for higher-resolution genotyping. We found that the occurrence of HLA-C*03:03*01 was increased in endometriosis than in control groups. Analysis of various KIR haplotypes revealed differences between the endometriosis and control cohorts. The number of KIR centromeric A/A haplotypes was increased in the endometriosis group than controls. Moreover, the endometriosis cohort was characterized by reduced number of KIR2DS2-positive individuals in the Han Chinese population. Our current findings suggest that the KIR and HLA-C genotypes are associated with the pathogenesis of endometriosis.
Visceral obesity and cell cycle pathways serve as links in the association between bisphenol A exposure and breast cancer
(2020-07-01)
Wang, Tsu-Nai
;
Yang, Pei-Jing
;
Tseng, Yu-Ting
;
Tsai, Yi-Shan
;
Kuo, Po-Lin
It has been identified that bisphenol A (BPA) exposure causes developmental toxicity in breast cells. However, the exact molecular mechanisms underlying the association between exposure to BPA and breast cancer remain unclear. The aim of the present study was to investigate the BPA-regulated signaling pathways associated with the aggressiveness and the development of breast cancer. Microarray technology and functional gene set analyses were used to evaluate BPA and breast cancer-associated biomarkers and pathways in a discovery-driven manner. Using individual dataset analyses, it was indicated that two BPA-associated gene sets, the visceral obesity pathway, involved in visceral fat deposits and the metabolic syndrome, and the cell cycle pathway, involved in cyclins and cell cycle regulation, were significantly associated with a high grade of aggressiveness and the development of estrogen receptor (ER)-positive breast cancer (between P<0.05 and 0.0001). The pooled analysis indicated that the most significant pathway was G(1)/S checkpoint regulation, and the cyclin and cell cycle regulation pathway for BPA-associated ER-positive cancer. Cancer cell signaling pathways were associated with healthy breast cells developing into breast cancer. The visceral obesity and the cell cycle pathways were indicated to link BPA exposure to breast cancer. The results of the present study demonstrate a significant association between breast cancer and BPA-regulated gene pathways.