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Updated: Aug 6, 2026

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Expression of nuclear insulin receptor substrate 1 in breast cancer
Diego Sisci1, Catia Morelli, Cecilia Garofalo
1Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende, Italy.
Background:
Insulin receptor substrate 1 (IRS-1), a cytoplasmic protein transmitting signals from the insulin and insulin-like growth factor 1 receptors, has been implicated in breast cancer. Previously, it was reported that IRS-1 can be translocated to the nucleus and modulate oestrogen receptor alpha (ERalpha) activity in vitro. However, the expression of nuclear IRS-1 in breast cancer biopsy specimens has never been examined.
Aims:
To assess whether nuclear IRS-1 is present in breast cancer and non-cancer mammary epithelium, and whether it correlates with other markers, especially ERalpha. Parallel studies were carried out for the expression of cytoplasmatic IRS-1.
Methods:
IRS-1 and ERalpha expression was assessed by immunohistochemical analysis. Data were evaluated using Pearson's correlation, linear regression and receiver operating characteristic analysis.
Results:
Median nuclear IRS-1 expression was found to be low in normal mammary epithelial cells (1.6%) and high in benign tumours (20.5%), ductal grade 2 carcinoma (11.0%) and lobular carcinoma (approximately 30%). Median ERalpha expression in normal epithelium, benign tumours, ductal cancer grade 2 and 3, and lobular cancer grade 2 and 3 were 10.5, 20.5, 65.0, 0.0, 80 and 15%, respectively. Nuclear IRS-1 and ERalpha positively correlated in ductal cancer (p<0.001) and benign tumours (p<0.01), but were not associated in lobular cancer and normal mammary epithelium. In ductal carcinoma, both nuclear IRS-1 and ERalpha negatively correlated with tumour grade, size, mitotic index and lymph node involvement. Cytoplasmic IRS-1 was expressed in all specimens and positively correlated with ERalpha in ductal cancer.
Conclusions:
A positive association between nuclear IRS-1 and ERalpha is a characteristic for ductal breast cancer and marks a more differentiated, non-metastatic phenotype.
Insights
Nuclear IRS-1 is present in breast cancer and correlates with ERalpha in ductal tumors, indicating a less aggressive cancer. This finding is crucial for understanding breast cancer progression and potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Insulin receptor substrate 1 (IRS-1) is a key signaling protein implicated in breast cancer.
- Nuclear translocation of IRS-1 and its modulation of oestrogen receptor alpha (ERalpha) have been observed in vitro.
- The presence of nuclear IRS-1 in human breast cancer biopsy specimens remains unexamined.
Purpose of the Study:
- To investigate the presence and significance of nuclear IRS-1 in breast cancer and normal mammary epithelium.
- To determine the correlation between nuclear IRS-1 and ERalpha expression in breast cancer.
- To assess the relationship between cytoplasmic IRS-1 and ERalpha.
Main Methods:
- Immunohistochemical analysis was employed to assess IRS-1 and ERalpha expression.
- Statistical evaluation included Pearson's correlation, linear regression, and receiver operating characteristic analysis.
Main Results:
- Nuclear IRS-1 expression was significantly higher in benign tumors and various breast cancer subtypes compared to normal epithelium.
- A positive correlation was observed between nuclear IRS-1 and ERalpha in ductal carcinoma and benign tumors.
- In ductal carcinoma, both nuclear IRS-1 and ERalpha negatively correlated with tumor grade, size, mitotic index, and lymph node involvement.
Conclusions:
- Nuclear IRS-1 and ERalpha co-expression is characteristic of ductal breast cancer.
- This association signifies a more differentiated and less metastatic tumor phenotype.
- Nuclear IRS-1 may serve as a potential biomarker for predicting breast cancer behavior.
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