Increased levels of circulating IGF-I does not initiate mammary tumorigenesis. A.) Kaplan-Meier tumor curve illustrating the percent of animals without mammary gland tumors vs. the day tumors were first palpated. Increased IGF-I had no effect on ErbB2 initiated mammary tumorigenesis (p = 0.59). Additionally, the moderate increase in circulating IGF-I did not induced mammary tumors in females expressing only the IGF-I transgene (purple) compared to controls (maroon line). B.) Increased circulating levels on IGF-I resulted in significantly higher (p < 0.05) IGF-I protein levels in tumors from bigenic females compared to tumors in ErbB2 transgenics (right panel). Middle panel shows IGF-I protein levels measured in contralateral normal mammary glands from these same bigenic and ErbB2 transgenic females. Left panel shows a significant increase (p < 0.05) in serum IGF-I in these same bigenic females compared to ErbB2 transgenics. Bars indicate the mean (±SEM) serum or protein levels of IGF-I assayed by ELISA. N = indicated with bars; MG = Mammary Gland; ErbB2 = ErbB2 transgenic only; Bigenic = TTR-IGF-I-ErbB2; MTTF (mean time to tumor formation) = weeks/days/months; * = p < 0.05.