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Updated: May 6, 2026
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Identification of gene expression signature in estrogen receptor positive breast carcinoma
Arvind D Thakkar1, Hemanth Raj, Debarshi Chakrabarti
1Department of Biomarker Discovery, Piramal Life Sciences Limited, Mumbai, Maharashtra, India.
Abstract:
A significant group of patient with estrogen receptor (ER) α positive breast tumors fails to appreciably respond to endocrine therapy. An increased understanding of the molecular basis of estrogen-mediated signal transduction and resultant gene expression may lead to novel strategies for treating breast cancer. In this study, we sought to identify the dysregulated genes in breast tumors related to ERα status. Microarray analyses of 31 tumor samples showed 108 genes differentially expressed in ERα (+) and ERα (-) primary breast tumors. Further analyses of gene lists indicated that a significant number of dysregulated genes were involved in mRNA transcription and cellular differentiation. The majority of these genes were found to have promoter-binding sites for E74-like factor 5 (ELF5; 54.6% genes), E2F transcription factor 1 (E2F1; 22.2% genes), and nuclear transcription factor Y alpha (NFYA; 32.4% genes). Six candidate genes (NTN4, SLC7A8, MLPH, ENPP1, LAMB2, and PLAT) with differential expression were selected for further validation studies using RT-qPCR (76 clinical specimen) and immunohistochemistry (48 clinical specimen). Our studies indicate significant over-expression of all the six genes in ERα (+) breast tumors as compared to ERα (-) breast tumors. In vitro studies using T-47D breast cancer cell line confirmed the estrogen dependant expression of four of the above six genes (SLC7A8, ENPP1, LAMB2, and PLAT). Collectively, our study provides further insights into the molecular basis of estrogen-dependent breast cancer and identifies "candidate biomarkers" that could be useful for predicting endocrine responsiveness.
Insights
Estrogen receptor alpha positive breast tumors resistant to endocrine therapy may have dysregulated genes. This study identified six key genes over-expressed in ERα (+) tumors, offering potential biomarkers for treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Many estrogen receptor (ER) α-positive breast tumors do not respond to endocrine therapy.
- Understanding estrogen-mediated signaling is crucial for developing new breast cancer treatments.
Purpose of the Study:
- To identify genes with altered expression in breast tumors based on ERα status.
- To explore the molecular basis of endocrine therapy resistance in breast cancer.
Main Methods:
- Microarray analysis of 31 tumor samples to identify differentially expressed genes.
- Validation of six candidate genes (NTN4, SLC7A8, MLPH, ENPP1, LAMB2, PLAT) using RT-qPCR and immunohistochemistry.
- In vitro studies in T-47D cells to confirm estrogen-dependent gene expression.
Main Results:
- 108 genes showed differential expression between ERα (+) and ERα (-) tumors.
- Dysregulated genes were primarily involved in mRNA transcription and cellular differentiation.
- Six selected genes (NTN4, SLC7A8, MLPH, ENPP1, LAMB2, PLAT) were significantly over-expressed in ERα (+) tumors.
- Estrogen-dependent expression confirmed for SLC7A8, ENPP1, LAMB2, and PLAT in vitro.
Conclusions:
- The study provides insights into the molecular mechanisms of estrogen-dependent breast cancer.
- Identified candidate biomarkers (SLC7A8, ENPP1, LAMB2, PLAT) may predict endocrine therapy responsiveness.
- Further research into these genes could lead to improved breast cancer treatment strategies.
