Related Experiment Video
Updated: Aug 31, 2025
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
Depletion of Mdig Changes Proteomic Profiling in Triple Negative Breast Cancer Cells
Chitra Thakur1,2,3, Nicholas J Carruthers4, Qian Zhang2
1Stony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, The State University of New York, Lauterbur Drive, Stony Brook, NY 11794, USA.
Abstract:
Triple-negative breast cancers are highly aggressive with an overall poor prognosis and limited therapeutic options. We had previously investigated the role of mdig, an oncogenic gene induced by some environmental risk factors, on the pathogenesis of breast cancer. However, a comprehensive analysis of the proteomic profile affected by mdig in triple-negative breast cancer has not been determined yet. Using label-free bottom-up quantitative proteomics, we compared wildtype control and mdig knockout MDA-MB-231 cells and identified the proteins and pathways that are significantly altered with mdig deletion. A total of 904 differentially expressed (p < 0.005) proteins were identified in the KO cells. Approximately 30 pathways and networks linked to the pathogenicity of breast cancer were either up- or downregulated, such as EIF2 signaling, the unfolded protein response, and isoleucine degradation I. Ingenuity Pathway Analysis established that the differentially expressed proteins have relevant biological actions in cell growth, motility, and malignancy. These data provide the first insight into protein expression patterns in breast cancer associated with a complete disruption of the mdig gene and yielded substantial information on the key proteins, biological processes, and pathways modulated by mdig that contribute to breast cancer tumorigenicity and invasiveness.
Insights
This study reveals how the mdig oncogene impacts triple-negative breast cancer by altering protein expression. Disrupting mdig significantly changes proteins involved in cell growth and malignancy, offering new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Triple-negative breast cancer (TNBC) is aggressive with poor prognosis and limited treatments.
- The oncogenic gene mdig, influenced by environmental factors, plays a role in breast cancer.
- A comprehensive proteomic analysis of mdig's impact on TNBC was previously lacking.
Purpose of the Study:
- To conduct a comprehensive proteomic analysis of mdig's role in triple-negative breast cancer.
- To identify proteins and pathways significantly altered by mdig deletion in TNBC cells.
- To understand the contribution of mdig-modulated proteins to breast cancer tumorigenicity and invasiveness.
Main Methods:
- Utilized label-free bottom-up quantitative proteomics.
- Compared wildtype control and mdig knockout MDA-MB-231 cell lines.
- Performed Ingenuity Pathway Analysis (IPA) on differentially expressed proteins.
Main Results:
- Identified 904 differentially expressed proteins (p < 0.005) in mdig knockout cells.
- Found approximately 30 significantly up- or downregulated pathways linked to breast cancer pathogenicity, including EIF2 signaling and unfolded protein response.
- IPA confirmed that altered proteins are critical for cell growth, motility, and malignancy.
Conclusions:
- This study provides the first detailed insight into protein expression changes following complete mdig gene disruption in breast cancer.
- Identified key proteins, biological processes, and pathways modulated by mdig that drive TNBC tumorigenicity and invasiveness.
- These findings may pave the way for novel therapeutic strategies targeting mdig in aggressive breast cancers.
