Insulin-like growth factor-1 (IGF1) pathway plays a critical role in malignant transformation, and epidemiology studies have also shown that single nucleotide polymorphisms (SNPs) in IGF1 pathway genes are associated with prostate cancer risk.
To investigate the role of the GH-IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we generated mice genetically predisposed to prostate cancer (the TRAMP model) to be homozygous for lit, a mutation that inactivates the GHRH receptor (GHRH-R) and reduces circulating levels of GH and IGF-I.
Overexpression of IGF-I occurs in tumors diagnosed in childhood (osteosarcoma, Wilms tumor, neuroblastoma, etc.) and in adults (breast, ovaries, colon and prostate cancer).
The adjusted odds ratios for having prostate cancer for patients with the GST-T1 and IGF-I variant alleles were 1.64 (95% confidence interval, 1.1-2.4; P = 0.01) and 1.70 (95% confidence interval, 1.1-2.7; P = 0.02), respectively.
It remains to be established whether IL-8 mediates certain effects of IGF-I on prostate cancer cells and whether differential responsiveness of prostate cancer cells to IGF-I relates to certain stages of prostate cancer.
Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel.
Background The inhibition of insulin-like growth factor receptor-1 (IGF-1R) induces cell cycle arrest and enhancing the effect of castration by delay of progression of human prostate cancer models.
IGF-I levels were significantly associated with PCa risk (P(trend) = 0.02) with a 21% increase of PCa risk when compared with the highest quartile to the lowest quartile.
Through identifying SNPs that are associated with QOL in men with prostate cancer and men from the general population, this study adds to the mapping of complex interrelationships that influence QOL and suggests a role for IGF-I in physical QOL outcomes.
Prostate cancer in Pten(-/-)Ptpn1(-/-) mice was characterized by increased cell proliferation and Akt activation, interpreted to reflect a heightened sensitivity to IGF-1 stimulation upon HFD feeding.
These results identify ZEB1 as a key transcriptional regulator of EMT in prostate cancer and suggest that the aberrant expression of ZEB1 in prostate cancer cells occurs in part in response to IGF-I stimulation.
Higher IGF1 circulating levels significantly increased 15% of cancer risk (odds ratio (OR), 1.15, 95% confidence interval (CI), 1.03-1.29), especially among prostate, pre-menopausal breast and colorectal cancer patients, whereas higher concentrations of IGFBP3 significantly decreased the risk of advanced prostate cancer by 56% (OR, 0.44, 95% CI, 0.25-0.77).
We explored possible interactions with body mass index and components in the IGF-1 pathway including IGFBP3, PI3k, and PTEN but none of these factors influenced the relation between IRS-1 genotype and prostate cancer risk.
One hypothesis is that the indirect insulin lowering effect may have an anti-neoplastic action as elevated insulin and insulin like growth factor - 1 (IGF-1) levels play a role in PCa development and progression.