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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #168317
Title: RAPID INDUCTION OF IGF-IR SIGNALING IN NORMAL AND TUMOR TISSUE FOLLOWING INTRAVENOUS INJECTION OF IGF-I IN MICE

Author
item LEE, A - BAYLOR COLL OF MEDICINE
item TAYLOR, S - ASTRA ZENECA, UK
item GREENALL, J - ASTRA ZENECA, UK
item MILLS, J - ASTRA ZENECA, UK
item TONGE, D - ASTRA ZENECA, UK
item ZHANG, P - BAYLOR COLL OF MEDICINE
item GEORGE, J - BAYLOR COLL OF MEDICINE
item FIOROTTO, M - BAYLOR COLL OF MEDICINE
item HADSELL, D - BAYLOR COLL OF MEDICINE

Submitted to: Hormone and Metabolic Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2003
Publication Date: 12/1/2003
Citation: Lee, A.V., Taylor, S.T., Greenall, J., Mills, J.D., Tonge, D.W., Zhang, P., George, J., Fiorotto, M.L., Hadsell, D.L. 2003. Rapid induction of igf-ir signaling in normal and tumor tissue following intravenous injection of igf-i in mice. Hormone and Metabolic Research. 35:651-655.

Interpretive Summary: The molecular mechanisms regulating hormone and growth factor signaling in normal animal tissue is poorly understood. In this paper we describe a procedure for measuring the IGF-I-dependent activation of signal transduction pathways within the normal mammary glands of mice. We found that intravenous injection IGF-I was very effective at activating defined signaling pathways both within the normal liver and mammary gland and within tumor cells growing in normal mice. This procedure may allow us to better understand signaling events within the context of normal animals.

Technical Abstract: The detection of IGF-IR signaling in animal models has important implications for determining the role of this receptor in normal physiology and tumor growth. While many reports have correlated changes in plasma IGF-I levels in vivo with biological responses, few have shown that altered IGF-I levels can directly affect signaling within normal or tumor tissue. Here, we present new data that shows how the intravenous (IV) injection of IGF-I can be used to directly examine IGF signaling at the tissue level. Tail-vein IV injection of IGF-I into mice resulted in a rapid and dose-dependent activation of the IGF-I receptor and downstream phosphorylation of Akt and ERK1/2 in liver, kidney, and mammary gland. Similarly, IV IGF-I rapidly stimulated signaling in HT-29 colorectal and in MCF-7 breast cancer xenografts. This study shows how IV IGF injection can be used to examine the signaling mechanisms used by IGF-IR, in both normal mammary tissue and during tumor growth, and may provide a model for the characterization of IGF inhibitors.