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Updated: Jul 16, 2026

In Vitro Evaluation of Oncogenic Transformation in Human Mammary Epithelial Cells
Published on: September 24, 2020
Primary cultured human breast epithelial cells up-regulate protein disulfide isomerase in response to zeranol
Michael Scott Updike1, Joseph C Sawdy, Li-Shu Wang
1Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA.
Background:
Experimental data at the molecular, cellular and organismal levels have implicated dietary components in cancer. Exposure to numerous growth factors, hormones and environmental agents, that can regulate signaling events, is involved in carcinogenesis. Research targets on gene-nutrient interactions may give useful information for the development of a novel diet-based intervention for the at-risk population.
Materials And Methods:
To examine the proteomic effect of a low level dietary compound on potential breast cancer, primary human breast epithelial cells were isolated and cultured in media with or without zeranol, an anabolic, non-estrogenic growth promoter with estrogenic activity, used in beef cattle and naturally found in some fungus in grain. The cells then underwent proteomic analysis.
Results:
2-D electrophoresis showed that protein disulfide isomerase (PDI) was up-regulated 5-fold in the breast epithelial cells exposed to zeranol. PDI has been shown to be up-regulated in a variety of cancerous tissues, although this is the first reported up-regulation of PDI in breast tissue.
Conclusion:
PDI may be a useful marker of dietary exposure to zeranol.
Insights
Zeranol, a compound found in grain, significantly increased protein disulfide isomerase (PDI) in human breast cells. This finding suggests PDI could serve as a biomarker for dietary zeranol exposure and potential breast cancer risk.
Area of Science:
- Molecular Biology
- Proteomics
- Cancer Research
Background:
- Dietary components are implicated in cancer development at multiple biological levels.
- Carcinogenesis involves signaling events regulated by growth factors, hormones, and environmental agents.
- Gene-nutrient interactions are crucial for developing dietary interventions for at-risk populations.
Purpose of the Study:
- To investigate the proteomic impact of zeranol, a dietary compound, on human breast epithelial cells.
- To assess zeranol's potential role in breast cancer development.
- To identify molecular markers associated with zeranol exposure.
Main Methods:
- Primary human breast epithelial cells were cultured in vitro.
- Cells were exposed to zeranol, a non-estrogenic growth promoter with estrogenic activity.
- Proteomic analysis, specifically 2-D electrophoresis, was employed to examine protein expression changes.
Main Results:
- Zeranol exposure led to a 5-fold up-regulation of protein disulfide isomerase (PDI).
- PDI is known to be elevated in various cancerous tissues.
- This study reports the first instance of PDI up-regulation in breast tissue due to zeranol exposure.
Conclusions:
- Protein disulfide isomerase (PDI) may function as a reliable biomarker for dietary zeranol exposure.
- Elevated PDI levels in breast tissue could indicate exposure to this dietary compound.
- Further research into PDI as a marker could inform dietary strategies for cancer prevention.

