Novel Transgenic Mouse Model for Testing the Effect of Circulating IGF- I on Mammary Stem/Progenitor Cell Number and Tumorigenesis

摘要

Epidemiological evidence indicates that high levels of circulating IGF-I (within the normal range) predict risk of breast cancer. To examine this experimentally, investigators have previously injected mice with IGF-I and shown that this increases mammary cancer incidence and progression. However, injection of IGF-I may create non-physiological peaks of IGF-I in the circulation. In this proposal we tested whether transgenic mice (TTR-IGF-I) that had a 30% increase in circulating levels of IGF-I (via liver specific expression) had altered ErbB2-induced mammary tumorigenesis. We found no difference in time to tumor formation in ErbB2 vs. TTR-IGF-I/ErbB2 transgenic mice. Our conclusion is either that ErbB2-induced tumorigenesis is insensitive to circulating IGF-I, or other studies using injected IGF-I were confounded by the transient spike in IGF-I caused by the non-physiologic method of administration. Further studies using additional mouse models are required to definitively address a role for circulating IGF-I in mammary tumorigenesis, however, our data suggest that the IGF-I may not directly regulate risk, but rather may be an indicator of another risk factor.