IGFBP-3 is known to possess intrinsic biological activities such as anti-tumor property in addition to its IGF/IGF-R axis-dependent actions in a variety of human cancers including breast cancer.
In this study we aimed to determine if two commonly used AAS, nandrolone and stanozolol, alone or in combination with IGF-I, could activate signaling involved in breast cancer cell proliferation.
We aimed to assess the association between IGF-I gene (CA repeats) polymorphism in breast cancer patients and their clinicopathological features, as well as disease recurrence and survival.
Recent studies on mechanisms of action of soy in breast cancer provide insights into epigenetic effects and the interaction of isoflavones with IGF-1 and with a number of polymorphisms of genes associated with breast cancer risk such as MDM2 and CYP1B1.
We used genomic technologies to better characterize the activity of the IGF axis in human breast cancer and to identify predictors of response to IGF targeted therapies.
Furthermore, absence of the wild-type-19 allele and alleles <(CA)19 were strongly associated with breast cancer (OR = 1.82; 95% CI = 1.20-2.77; P = 0.005 and OR = 1.70; 95% CI = 1.19-2.43; P = 0.003, respectively).
We previously reported an insulin-like growth factor (IGF) gene expression signature, based on genes induced or repressed by IGF-I, which correlated with poor prognosis in breast cancer.
Finally, an insulin/IGF-I gene expression signature predicted recurrence-free survival in patients with ER(+) breast cancer treated with the antiestrogen tamoxifen.
We found a reverse-correlation between the expression of miR-145 and its target genes, such as fascin-1, c-myc, SMAD2/3 and IGF-1R in breast cancer cell lines and breast cancer patient tissues.
Insulin-like growth factor receptor 1 (IGF-1R) is a receptor protein tyrosine kinase that is activated by ligand (IGF-1) binding and promotes mitogenic, metastatic, and antiapoptotic phenotypes of breast cancer.
Insulin like growth factor-1 (IGF-1) was chosen because it is highly relevant in breast cancer and because measuring serum IGF-1 levels by conventional methods is complicated due to specific IGF-1 serum binding proteins.
Women (n = 14) with any rare variant block1 diplotype had higher odds to be BRCA1 mutation carriers OR 4.1 (95% CI 1.4-12.2), to lack the common IGF1 19 CA-repeat allele OR 33.3 (95% CI 6.6-166.7), and were more likely to develop early-onset breast cancer (Log Rank P < 0.001) than women with common block1 diplotypes.
IGF-1R signaling is important for the survival of breast cancer cells and crosstalk between IGF-1R and EGFR signaling pathways have been implicated in the development of more aggressive disease.
Our results show for the first time that E2 and IGF-1 inhibit PAR-4 gene expression in MCF-7 cells, suggesting that this down-regulation may provide a selective advantage for breast cancer cell survival.
Of the six selected SNPs, only one IGF-I SNP (rs7965399) was associated with breast cancer risk in a recessive model (OR = 1.86; 95% CI: 1.04-3.32), and the association was more evident in patients who had menopause under age 50 or ER negative tumors.