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Profiling of gene expression regulated by 17?-estradiol and tamoxifen in estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines.

ABSTRACT: One area of great importance in breast cancer (BC) research is the study of gene expression regulated by both estrogenic and antiestrogenic agents. Although many studies have been performed in this area, most of them have only addressed the effects of 17?-estradiol (E2) and tamoxifen (TAM) on MCF7 cells. This study aimed to determine the effect of low doses of E2 and TAM on the expression levels of 84 key genes, which are commonly involved in breast carcinogenesis, in four BC cell lines differentially expressing estrogen receptor (ER) ? and HER2 (MCF7, T47D, BT474, and SKBR3). The results allowed us to determine the expression patterns modulated by E2 and TAM in ER?+ and ER?- cell lines, as well as to identify differences in expression patterns. Although the MCF7 cell line is the most frequently used model to determine gene expression profiles in response to E2 and TAM, the changes in gene expression patterns identified in ER?+ and ER?- cell lines could reflect distinctive properties of these cells. Our results could provide important markers to be validated in BC patient samples, and subsequently used for predicting the outcome in ER?+ and ER?- tumors after TAM or hormonal therapy. Considering that BC is a molecularly heterogeneous disease, it is important to understand how well, and which cell lines, best model that diversity.

SUBMITTER: Rangel N

PROVIDER: S-EPMC5614746 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Profiling of gene expression regulated by 17β-estradiol and tamoxifen in estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines.

Rangel Nelson N Villegas Victoria E VE Rondón-Lagos Milena M

Breast cancer (Dove Medical Press) 20170920

One area of great importance in breast cancer (BC) research is the study of gene expression regulated by both estrogenic and antiestrogenic agents. Although many studies have been performed in this area, most of them have only addressed the effects of 17β-estradiol (E2) and tamoxifen (TAM) on MCF7 cells. This study aimed to determine the effect of low doses of E2 and TAM on the expression levels of 84 key genes, which are commonly involved in breast carcinogenesis, in four BC cell lines differen ...[more]

PMID: 29033607

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Project description:Estrogen receptor-positive and human epidermal growth factor receptor 2-negative (ER+ HER2- ) breast cancer accounts for ~ 60-70% of all cases of invasive breast carcinoma. High-grade ER+ HER2- tumors respond poorly to endocrine therapy. In this study, we systematically analyzed clinical and multi-omics data to find potential strategies for personalized therapy of patients with high-grade ER+ HER2- disease. Six different cohorts were analyzed, for which multi-omics data were available. Grade III ER+ HER2- cases harbored higher proportions of large tumor size (> 5 cm), lymph node metastasis, chemotherapy use, and luminal B subtypes defined by PAM50, as compared with grade I/II tumors. DNA methylation (HM450) data and methylation-specific PCR indicated that the cg18629132 locus in the MKI67 promoter was hypermethylated in grade I/II cases and normal tissue, but hypomethylated in grade III cases or triple-negative breast cancer, resulting in higher expression of MKI67. Mutations in ESR1 and TP53 were detected in post-endocrine treatment metastatic samples at a higher rate than in treatment-naive tumors in grade III cases. We identified 42 and 20 focal copy number events in nonmetastatic and metastatic high-grade ER+ HER2- cases, respectively, with either MYC or MDM2 amplification representing an independent prognostic event in grade III cases. Transcriptional profiling within grade III tumors highlighted ER signaling downregulation and upregulation of immune-related pathways in non-luminal-like tumors defined by PAM50. Recursive partitioning analysis was employed to construct a decision tree of an endocrine-resistant subgroup (GATA3-negative and AGR-negative) of two genes that was validated by immunohistochemistry in a Chinese cohort. All together, these data suggest that grade III ER+ HER2- tumors have distinct clinical and molecular characteristics compared with low-grade tumors, particularly in cases with non-luminal-like biology. Due to the dismal prognosis in this group, clinical trials are warranted to test the efficacy of potential novel therapies.

Dataset Information

Profiling of gene expression regulated by 17?-estradiol and tamoxifen in estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines.

Publications

Profiling of gene expression regulated by 17β-estradiol and tamoxifen in estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines.

Similar Datasets

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