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. 2004 Apr;84(3):225-33. doi: 10.1023/B:BREA.0000019954.59130.d3.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / physiopathology*
  • Case-Control Studies
  • Female
  • Gene Expression Profiling*
  • Genetic Predisposition to Disease*
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor II / analysis
  • Insulin-Like Growth Factor II / biosynthesis*
  • Life Style
  • Middle Aged
  • Pedigree
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis*
  • Risk Factors

Substances

  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II