Insulin-like growth factor (IGF)-system mRNA quantities in normal and tumor breast tissue of women with sporadic and familial breast cancer risk.
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.
Voskuil
Dorien W
DW
Division of Experimental Therapy, The Netherlands Cancer Institute, The Netherlands.
Bosma
Astrid
A
Vrieling
Alina
A
Rookus
Matti A
MA
van 't Veer
Laura J
LJ
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000096:biosynthesis*; D008019:Life Style; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D012307:Risk Factors
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II