MICaB Graduate Program
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Douglas Yee, M.D.
Department of Medicine
University of Chicago, 1981, M.D.
Growth regulation of breast cancer
Our laboratory is interested in understanding the contribution
of insulin-like growth factor (IGF) action to the breast cancer
malignant phenotype. We have shown that IGF-I can stimulate
cell growth, enhance survival, and stimulate motility and
adhesion. Activation of specific substrates, insulin receptor
substrate-1 (IRS-1) and IRS-2 are associated with either cell
proliferation or cell motility. A major focus of the laboratory
is to elucidate the signals downstream of these two adaptor
proteins that account for the observed phenotype. In breast
cancer, development of therapeutics designed to target specific
growth regulatory molecules has proven to be remarkably successful
in the clinic. Since the IGFs regulate several important breast
cancer phenotypes, the second focus of the laboratory is to
develop anti-IGF strategies that have potential as cancer
therapeutics. Our long-term goal is to improve breast cancer
treatment by understanding and targeting the key components
of the IGF system.
Selected Recent Publications:
- Miller BS and Yee D. The type I IGF receptor (IGF1R) as a therapeutic target in cancer. Cancer Res, in press.
- Sachdev D, Singh R, Fujita-Yamaguchi Y, Yee D. 2006. Down-regulation of insulin receptor by antibodies against the type I insulin-like growth factor receptor: implications for anti-insulin-like growth factor therapy in breast cancer. Cancer Res 66:2391-2402.
- Kirstein MN, Brundage RC, Elmquist WF, Remmel RP, Marker PH, Guire DE, Yee D. 2006. Characterization of an in vitro cell culture bioreactor system to evaluate anti-neoplastic drug regimens. Breast Cancer Res Treat 96:217-225.
- Farooqui M, Geng ZH, Stephenson EJ, Zaveri N, Yee D, Gupta K. 2006. Naloxone acts as an antagonist of estrogen receptor activity in MCF-7 cells. Mol Cancer Ther 5:611-620.
- Zhang X, Lin M, van Golen KL, Yoshioka K, Itoh K, Yee D. 2005. Multiple signaling pathways are activated during insulin-like growth factor-I (IGF-I) stimulated breast cancer cell migration. Breast Cancer Res Treat 93:159-168.
- Zhang S, Kamaraju S, Hakuno F, Kabuta T, Takahashi S-I, Sachdev D, Yee D. 2004. Motility response to insulin-like growth factor-I in MCF-7 cells is associated with IRS-2 activation and integrin expression. Breast Canc Res Treat, 83:161-170.
- Hoang CD, Zhang X, Scott PD, Guillaume TJ, Maddaus MA, Yee D, Kratzke RA. 2004. Selective activation of insulin receptor substrate-1 and -2 in pleural mesothelioma cells: association with distinct malignant phenotypes. Cancer Res 64:7479-7485.
- Sachdev D, Hartell JS, Lee AV, Zhang X, Yee D. 2004. A dominant negative type I insulin-like growth factor-1 inhibits metastasis of human cancer cells. J Biol Chem 279:5017-5024.
Last updated: October 4, 2005