Peptide concentrations and mRNA expression of IGF-I, IGF-II and IGFBP-3 in breast cancer and their associations with disease characteristics

Breast Cancer Res Treat. 2009 May;115(1):151-62. doi: 10.1007/s10549-008-0046-x. Epub 2008 May 15.


Purpose: To measure peptide concentrations and mRNA expression of the IGF Family in breast cancer and to examine their associations with the disease features.

Experimental design: Fresh tumor samples were collected from 348 patients who underwent surgery for breast cancer. Tissue levels of mRNA and peptide of IGF-I, IGF-II, and IGFBP-3 were analyzed with real-time RT-PCR and ELISA, respectively. Cox proportional hazards regression model was used to examine the associations of IGF markers with patient survival.

Results: Age was inversely associated with IGF-I, IGF-II and IGFBP-3 at both mRNA and peptide levels. Small tumors, early TNM stages, or low grades were associated with high mRNA expression of IGFs and IGFBP-3. Hormone receptors were positively correlated with IGF-I and IGF-II expression. Survival analysis showed that patients with high expression of one of the IGF-I transcripts, IGF-IA, had lower risk of disease recurrence (HR = 0.47, 95%CI: 0.27-0.81) and death (HR = 0.35, 95%CI: 0.18-0.70) compared to those with low expression. High IGFBP-3 expression was also inversely associated with reduced risk of death (HR = 0.47, 95%CI: 0.23-0.95). Similar associations, however, were not observed when tissue levels of IGF-I peptide or IGFBP-3 protein were analyzed. High IGF-II peptide was related to increased risk of relapse (HR = 1.91, 95%CI: 1.12-3.27).

Conclusion: Our findings of high mRNA expression of IGFs and IGFBP-3 being associated with less aggressive tumors and favorable prognosis were consistent with previous observations, but were not supported by the measurement of tissue levels of IGF-I peptide and IGFBP-3 protein, suggesting that IGF mRNA expression and tissue levels of IGF peptides are regulated by different mechanisms and assessing these molecules in tumor tissue may have different implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / biosynthesis*
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor II / biosynthesis*
  • Middle Aged
  • Peptides / chemistry
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / metabolism*
  • Recurrence


  • Insulin-Like Growth Factor Binding Protein 3
  • Peptides
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II