TY - JOUR
T1 - Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer
T2 - Correlation with clinical parameters and disease-free survival
AU - Rocha, Rafael L.
AU - Hilsenbeck, Susan G.
AU - Jackson, James G.
AU - VanDenBerg, Carla L.
AU - Weng, Chye Ning
AU - Lee, Adrian V.
AU - Yee, Douglas
PY - 1997
Y1 - 1997
N2 - 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 ≤2 cm (P = 0.04), and for patients with estrogen receptor-positive tumors, there was a trend toward worse DFS (P = 0.06). These results suggest that higher tumor levels of IGFBP-3 are associated with worse features in breast cancer. However, IGFBP-3 was not an independent prognostic factor. In contrast, high levels of IRS-1 in the tumors predicted a higher incidence of recurrence, suggesting that IRS-1-mediated signaling in breast tumors may be involved in the growth regulation of breast cancer.
AB - 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 ≤2 cm (P = 0.04), and for patients with estrogen receptor-positive tumors, there was a trend toward worse DFS (P = 0.06). These results suggest that higher tumor levels of IGFBP-3 are associated with worse features in breast cancer. However, IGFBP-3 was not an independent prognostic factor. In contrast, high levels of IRS-1 in the tumors predicted a higher incidence of recurrence, suggesting that IRS-1-mediated signaling in breast tumors may be involved in the growth regulation of breast cancer.
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M3 - Article
C2 - 9815544
AN - SCOPUS:0031051830
SN - 1078-0432
VL - 3
SP - 103
EP - 109
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -