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Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer: correlation with
R L Rocha1, S G Hilsenbeck, J G Jackson
1Department of Medicine, Division of Medical Oncology, University of Texas Health Science Center at San Antonio, Texas 78284-7884, USA.
Abstract:
Insulin-like growth factors (IGFs) interact with specific cell surface receptors to mediate cell growth. Intracellular effects of the IGFs are mediated by activation of secondary messenger molecules. One of these proteins, insulin receptor substrate-1 (IRS-1), is phosphorylated after type I IGF receptor activation and has a major role in IGF signaling. Receptor activation also is influenced by high-affinity IGF binding proteins (IGFBPs). In serum, IGFBP-3 is the predominant species. The role of IGFBP-3 in the regulation of breast cancer cell growth is unclear; both growth inhibition and stimulation have been documented in tissue culture systems. To investigate the influence of IGFBP-3 and IRS-1 in breast cancer, we measured levels of these proteins by ELISA and immunoblotting in 195 node-negative primary human breast cancers and compared their levels with known prognostic factors and disease-free survival (DFS). IGFBP-3 levels correlated positively with tumor size (r = 0.27, P < 0.0001) and negatively with estrogen receptor (r = -0.35, P < 0. 0001) and progesterone receptor (r = -0.16, P = 0.021). In contrast, IRS-1 did not correlate with prognostic factors, but higher levels of IRS-1 predicted worse DFS for the subset of patients with tumors
Insights
Higher levels of insulin-like growth factor-binding protein 3 (IGFBP-3) correlate with adverse breast cancer features. However, insulin receptor substrate-1 (IRS-1) shows potential as a prognostic marker, with higher IRS-1 levels predicting worse disease-free survival in specific patient subsets.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Insulin-like growth factors (IGFs) regulate cell growth via cell surface receptors.
- Insulin receptor substrate-1 (IRS-1) is crucial for intracellular IGF signaling.
- IGF binding proteins (IGFBPs), particularly IGFBP-3, modulate IGF receptor activation, but their role in breast cancer is debated.
Purpose of the Study:
- To investigate the association of IGFBP-3 and IRS-1 levels with prognostic factors and disease-free survival (DFS) in primary human breast cancers.
- To determine the potential prognostic value of IGFBP-3 and IRS-1 in breast cancer.
Main Methods:
- Quantification of IGFBP-3 and IRS-1 protein levels using ELISA and immunoblotting in 195 node-negative primary breast cancer tissues.
- Correlation analysis of protein levels with established prognostic factors (tumor size, estrogen/progesterone receptor status).
- Analysis of the relationship between protein levels and disease-free survival (DFS).
Main Results:
- IGFBP-3 levels positively correlated with tumor size and negatively with estrogen and progesterone receptor expression.
- IRS-1 levels did not correlate with prognostic factors.
- Elevated IRS-1 levels were associated with worse DFS in patients with tumors ≤2 cm and a trend towards worse DFS in estrogen receptor-positive tumors.
Conclusions:
- High tumor levels of IGFBP-3 are linked to unfavorable breast cancer characteristics but are not an independent prognostic factor.
- Elevated IRS-1 levels in tumors predict an increased risk of recurrence, suggesting its involvement in breast cancer growth regulation.