Peptide concentrations and mRNA expression of IGF-I, IGF-II and IGFBP-3 in breast cancer and their associations with disease characteristics.
OBJECTIVE
To measure peptide concentrations and mRNA expression of the IGF Family in breast cancer and to examine their associations with the disease features.


METHODS
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).


CONCLUSIONS
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.
Mu
Lina
L
Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
Katsaros
Dionyssios
D
Wiley
Andrew
A
Lu
Lingeng
L
de la Longrais
Irene A Rigault
IA
Smith
Stephanie
S
Khubchandani
Sapna
S
Sochirca
Olga
O
Arisio
Riccardo
R
Yu
Herbert
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism*; D012008:Recurrence
D018972:Insulin-Like Growth Factor Binding Protein 3; D010455:Peptides; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II