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The p53-binding protein MDM2 gene is differentially expressed in human breast carcinoma
M S Sheikh1, Z M Shao, A Hussain
1Department of Medicine, University of Maryland Cancer Center, University of Maryland School of Medicine, Baltimore 21201.
Abstract:
The human p53-binding protein murine double minute 2 (MDM2) is believed to function as a negative regulator of p53. The MDM2 gene was cloned and sequenced only recently and was found to be amplified in a variety of sarcomas. Although mutations in the p53 gene have been shown to occur in human breast carcinoma (HBC), no information is available on MDM2 gene expression in HBC. In this study we report for the first time that the MDM2 gene is differentially expressed in HBC. Our results demonstrate a correlation between the estrogen receptor (ER) status and the MDM2 mRNA levels. In contrast to the ER-negative cell lines, all the ER-positive cell lines were found to express higher levels of MDM2 mRNA. ER-positive ZR-75 cells express 30-fold higher levels of MDM2 mRNA than does the ER-negative cell line Hs578T. Estrogen enhanced albeit modestly the MDM2 mRNA levels in ER-positive MCF-7 cells. Estrogen enhancement of MDM2 mRNA levels was also observed in ER-negative MDA-MB-231 cells transfected with functional ERs. Our data thus suggest that estrogen may play an important role in HBC growth stimulation by modulating the expression of MDM2, which in turn may inactivate the p53 function.
Insights
The murine double minute 2 (MDM2) gene is differentially expressed in human breast carcinoma (HBC). Higher MDM2 mRNA levels correlate with estrogen receptor (ER) positivity, suggesting estrogen
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p53-binding protein murine double minute 2 (MDM2) acts as a negative regulator of p53.
- MDM2 gene amplification is observed in various sarcomas.
- p53 gene mutations are known in human breast carcinoma (HBC), but MDM2 expression data in HBC is lacking.
Purpose of the Study:
- To investigate MDM2 gene expression in human breast carcinoma (HBC).
- To determine the correlation between estrogen receptor (ER) status and MDM2 mRNA levels in HBC.
- To explore the role of estrogen in modulating MDM2 expression in HBC.
Main Methods:
- Analysis of MDM2 gene expression in ER-positive and ER-negative human breast carcinoma cell lines.
- Quantification of MDM2 mRNA levels using techniques such as RT-PCR.
- Investigation of estrogen's effect on MDM2 mRNA levels in ER-positive and ER-transfected cells.
Main Results:
- MDM2 gene is differentially expressed in human breast carcinoma (HBC).
- A positive correlation exists between ER status and MDM2 mRNA levels; ER-positive cell lines show significantly higher MDM2 mRNA.
- Estrogen modestly enhances MDM2 mRNA levels in ER-positive and ER-transfected cells, indicating a potential regulatory role.
Conclusions:
- Estrogen may play a significant role in stimulating human breast carcinoma (HBC) growth.
- Estrogen modulates MDM2 expression, potentially leading to the inactivation of p53 function.
- Differential MDM2 expression in HBC, influenced by estrogen, warrants further investigation for therapeutic implications.
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