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Comparison and identification of estrogen-receptor related gene expression profiles in breast cancer of different ethnic origins.

ABSTRACT: The interactions between genetic variants in estrogen receptor (ER) have been identified to be associated with an increased risk of breast cancer. Available evidence indicates that genetic variance within a population plays a crucial role in the occurrence of breast cancer. Thus, the comparison and identification of ER-related gene expression profiles in breast cancer of different ethnic origins could be useful for the development of genetic variant cancer therapy. In this study, we performed microarray experiment to measure the gene expression profiles of 59 Taiwanese breast cancer patients; and through comparative bioinformatics analysis against published U.K. datasets, we revealed estrogen-receptor (ER) related gene expression between Taiwanese and British patients. In addition, SNP databases and statistical analysis were used to elucidate the SNPs associated with ER status. Our microarray results indicate that the expression pattern of the 65 genes in ER+ patients was dissimilar from that of the ER- patients. Seventeen mutually exclusive genes in ER-related breast cancer of the two populations with more than one statistically significant SNP in genotype and allele frequency were identified. These 17 genes and their related SNPs may be important in population-specific ER regulation of breast cancer. This study provides a global and feasible approach to study population-unique SNPs in breast cancer of different ethnic origins.

SUBMITTER: Chen HW

PROVIDER: S-EPMC3091396 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Comparison and identification of estrogen-receptor related gene expression profiles in breast cancer of different ethnic origins.

Chen Hsiao-Wei HW Huang Hsuan-Cheng HC Lin Yi-Shing YS Chang King-Jen KJ Kuo Wen-Hung WH Hwa Hsiao-Lin HL Hsieh Fon-Jou FJ Juan Hsueh-Fen HF

Breast cancer : basic and clinical research 20080325

The interactions between genetic variants in estrogen receptor (ER) have been identified to be associated with an increased risk of breast cancer. Available evidence indicates that genetic variance within a population plays a crucial role in the occurrence of breast cancer. Thus, the comparison and identification of ER-related gene expression profiles in breast cancer of different ethnic origins could be useful for the development of genetic variant cancer therapy. In this study, we performed mi ...[more]

PMID: 21655371

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Project description:BackgroundDirectly comparing gene expression profiles of estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancers cannot determine whether differentially expressed genes between these two subtypes result from dysregulated expression in ER+ cancer or ER- cancer versus normal controls, and thus would miss critical information for elucidating the transcriptomic difference between the two subtypes.Principal findingsUsing microarray datasets from TCGA, we classified the genes dysregulated in both ER+ and ER- cancers versus normal controls into two classes: (i) genes dysregulated in the same direction but to a different extent, and (ii) genes dysregulated to opposite directions, and then validated the two classes in RNA-sequencing datasets of independent cohorts. We showed that the genes dysregulated to a larger extent in ER+ cancers than in ER- cancers enriched in glycerophospholipid and polysaccharide metabolic processes, while the genes dysregulated to a larger extent in ER- cancers than in ER+ cancers enriched in cell proliferation. Phosphorylase kinase and enzymes of glycosylphosphatidylinositol (GPI) anchor biosynthesis were upregulated to a larger extent in ER+ cancers than in ER- cancers, whereas glycogen synthase and phospholipase A2 were downregulated to a larger extent in ER+ cancers than in ER- cancers. We also found that the genes oppositely dysregulated in the two subtypes significantly enriched with known cancer genes and tended to closely collaborate with the cancer genes. Furthermore, we showed the possibility that these oppositely dysregulated genes could contribute to carcinogenesis of ER+ and ER- cancers through rewiring different subpathways.ConclusionsGPI-anchor biosynthesis and glycogenolysis were elevated and hydrolysis of phospholipids was depleted to a larger extent in ER+ cancers than in ER- cancers. Our findings indicate that the genes oppositely dysregulated in the two subtypes are potential cancer genes which could contribute to carcinogenesis of both ER+ and ER- cancers through rewiring different subpathways.

Project description:BACKGROUND:Breast cancer (BC) is highly heterogeneous with ~?60-70% of estrogen receptor positive BC patient's response to anti-hormone therapy. Estrogen receptors (ERs) play an important role in breast cancer progression and treatment. Estrogen related receptors (ERRs) are a group of nuclear receptors which belong to orphan nuclear receptors, which have sequence homology with ERs and share target genes. Here, we investigated the possible role and clinicopathological importance of ERR? in breast cancer. METHODS:Estrogen related receptor ? (ERR?) expression was examined using tissue microarray slides (TMA) of Breast Carcinoma patients with adjacent normal by immunohistochemistry and in breast cancer cell lines. In order to investigate whether ERR? is a direct target of ER?, we investigated the expression of ERR? in short hairpin ribonucleic acid knockdown of ER? breast cancer cells by western blot, qRT-PCR and RT-PCR. We further confirmed the binding of ER? by electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), Re-ChIP and luciferase assays. Fluorescence-activated cell sorting analysis (FACS) was performed to elucidate the role of ERR? in cell cycle regulation. A Kaplan-Meier Survival analysis of GEO dataset was performed to correlate the expression of ERR? with survival in breast cancer patients. RESULTS:Tissue microarray (TMA) analysis showed that ERR? is significantly down-regulated in breast carcinoma tissue samples compared to adjacent normal. ER?+?ve breast tumors and cell lines showed a significant expression of ERR? compared to ER-ve tumors and cell lines. Estrogen treatment significantly induced the expression of ERR? and it was ER? dependent. Mechanistic analyses indicate that ER? directly targets ERR? through estrogen response element and ERR? also mediates cell cycle regulation through p18, p21cip and cyclin D1 in breast cancer cells. Our results also showed the up-regulation of ERR? promoter activity in ectopically co-expressed ER? and ERR? breast cancer cell lines. Fluorescence-activated cell sorting analysis (FACS) showed increased G0/G1 phase cell population in ERR? overexpressed MCF7 cells. Furthermore, ERR? expression was inversely correlated with overall survival in breast cancer. Collectively our results suggest cell cycle and tumor suppressor role of ERR? in breast cancer cells which provide a potential avenue to target ERR? signaling pathway in breast cancer. CONCLUSION:Our results indicate that ERR? is a negative regulator of cell cycle and a possible tumor suppressor in breast cancer. ERR? could be therapeutic target for the treatment of breast cancer.

Project description:BackgroundWesternization and etiologic heterogeneity may play a role in the rising breast cancer incidence in Asian American (AA) women. We report breast cancer incidence in Asian-origin populations.MethodsUsing a specialized Surveillance, Epidemiology, and End Results-9 Plus API Database (1990-2014), we analyzed breast cancer incidence overall, by estrogen receptor (ER) status, and age group among non-Hispanic white (NHW) and AA women. We used age-period-cohort models to assess time trends and quantify heterogeneity by ER status, race and ethnicity, and age.ResultsOverall, breast cancer incidence increased for most AA ethnicities (Filipina: estimated annual percentage change [EAPC] = 0.96%/year, 95% confidence interval [CI] = 0.61% to 1.32%; South Asian: EAPC = 1.68%/year, 95% CI = 0.24% to 3.13%; Chinese: EAPC = 0.65%/year, 95% CI = 0.03% to 1.27%; Korean: EAPC = 2.55%/year, 95% CI = 0.13% to 5.02%; and Vietnamese women: EAPC = 0.88%/year, 95% CI = 0.37% to 1.38%); rates did not change for NHW (EAPC = -0.2%/year, 95% CI = -0.73% to 0.33%) or Japanese women (EAPC = 0.22%/year, 95% CI = -1.26% to 1.72%). For most AA ethnicities, ER-positive rates statistically significantly increased, whereas ER-negative rates statistically significantly decreased. Among older women, ER-positive rates were stable for NHW and Japanese women. ER-negative rates decreased fastest in NHW and Japanese women among both age groups.ConclusionsIncreasing ER-positive incidence is driving an increase overall for most AA women despite declining ER-negative incidence. The similar trends in NHW and Japanese women (vs other AA ethnic groups) highlight the need to better understand the influences of westernization and other etiologic factors on breast cancer incidence patterns in AA women. Heterogeneous trends among AA ethnicities underscore the importance of disaggregating AA data and studying how breast cancer differentially affects the growing populations of diverse AA ethnic groups.

Dataset Information

Comparison and identification of estrogen-receptor related gene expression profiles in breast cancer of different ethnic origins.

Publications

Comparison and identification of estrogen-receptor related gene expression profiles in breast cancer of different ethnic origins.

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