The mitogenic effects of insulin-like growth factors (IGFs) are regulated by a family of insulin-like growth factor binding proteins (IGFBPs). One member of this family, IGFBP-3, mediates the growth-inhibitory and apoptosis-inducing effects of a number of growth factors and hormones such as transfor
Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer
✍ Scribed by Peter F. Bruning; Jaap Van Doorn; Johannes M. G. Bonfrèr; Paul A. M. Van Noord; Catharina M. Korse; Theodora C. Linders; Augustinus A. M. Hart
- Book ID
- 102864833
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- French
- Weight
- 595 KB
- Volume
- 62
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Insulin
-like growth factor I (IGF-I) is a potent mitogen for human breast-cancer cells in vitro. In circulation, most of IGF-I is bound to IGF-binding protein 3 (IGFBP-3). This high-affinity binding is thought to have an important limiting effect on the availability of IGF-I for biological activity. To assess the availability of IGF-I for receptor binding, we determined serum levels of IGF-I and IGFBP-3 and IGF-I/IGFBP-3 ratios. In a case-control study, I50 women aged 38 to 75 years presenting with stage-I or -11 breast cancer were investigated just prior to surgery (n = 76), or to irradiation one month after surgery (n = 74). The population-based control group consisted of 441 women of the same age having no breast cancer. Women reporting diabetes mellitus or other hormonal abnormalities were excluded. Premenopausal cases showed elevated IGF-I serum concentrations, decreased IGFBP-3 levels and increased IGF-I/IGFBP-3 ratios. The IGF-I/IGFBP-3 ratio was a significant breast-cancer risk factor, also after adjustment for age, family history, height, body-mass index, body-fat distribution, and serum levels of C-peptide. The relative risk was 7.34 for the highest compared with the lowest quintile of IGF-IIIGFBP-3. The presence or absence of tumor had no influence on these results. Increased levels of available IGF-I in the circulation of pre-menopausal women may contribute to the development of breast cancer.
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