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Insulin-Like Growth Factor (IGF)-System mRNA Quantities in Normal and Tumor Breast Tissue of Women with Sporadic and Familial Breast Cancer Risk

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Abstract

The insulin-like growth factor (IGF)-system plays a role in breast cancer susceptibility as well as in growth and progression of breast carcinomas. So far, findings have been based on serum IGF-I levels and semi-quantitative assessment of IGF-system expression levels in model systems and human tissue. Quantitative data on mRNA expression in different types of human breast tissue are lacking. Breast tissue samples (n= 83) were available from 72 women. Messenger RNA expression of IGF-I, IGF-II, and their receptors (IGF-1R and IGF-2R) was assessed by real-time RT-PCR. We found a large variation in mRNA levels. Expression of each gene was significantly higher in normal tissue than in tumor tissue (median for normal and tumor tissue, respectively (arbitrary units); IGF-I: 25.2 and 1.4; IGF-II: 5.9 and 0.6; IGF-1R: 0.18 and 0.07; IGF-2R: 1.8 and 0.9; p < 0.0001, Mann–Whitney test). Interestingly, in tumor tissue from patients with a strong family history of breast cancer, expression of both receptors was higher than in sporadic patients (IGF-1R: 0.13 and 0.05, p= 0.04; IGF-2R: 1.1 and 0.8, p= 0.04). For cancer-free controls, expression of IGF-II and IGF-2R in normal breast tissue was also higher in women with a family history of breast cancer than in women without such a family history (IGF-II: 7.2 and 1.5, p= 0.02; IGF-2R: 2.6 and 1.5, p= 0.09). Our study quantitatively shows that mRNA expression levels of IGF-system components in the breast are generally higher in normal tissue compared with tumor tissue, and higher in tissue from women with a family history of breast cancer. A basis has therefore been created for studies aimed at understanding IGF as a breast cancer risk factor, the relationship between IGF-systems in serum and tissues, and effects of lifestyle factors on the IGF-system.

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Authors and Affiliations

  1. Division of Experimental Therapy, The Netherlands Cancer Institute, The Netherlands

    Dorien W. Voskuil, Astrid Bosma & Alina Vrieling

  2. Department of Epidemiology, The Netherlands Cancer Institute, The Netherlands

    Dorien W. Voskuil & Matti A. Rookus

  3. Department of Pathology, The Netherlands Cancer Institute, The Netherlands

    Laura J. van't Veer

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  1. Dorien W. Voskuil
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  2. Astrid Bosma
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  5. Laura J. van't Veer
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Voskuil, D.W., Bosma, A., Vrieling, A. et al. Insulin-Like Growth Factor (IGF)-System mRNA Quantities in Normal and Tumor Breast Tissue of Women with Sporadic and Familial Breast Cancer Risk. Breast Cancer Res Treat 84, 225–233 (2004). https://doi.org/10.1023/B:BREA.0000019954.59130.d3

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