Youngman Oh

Ph.D., Stanford University, 1994
Associate Professor of Pediatrics
Joint Assistant Professor, Cell and Developmental Biology

Breast carcinoma and other solid tumors such as prostate, ovarian, and lung, are the major causes of cancer mortality, and new approaches to their treatment are desperately needed. The insulin-like growth factors (IGFs) are major regulators of epithelial cell growth, and virtually all breast (and many other types of solid) tumor specimens express the IGFs and their transmembrane receptors. By comparison, relatively little is known about the role of the third component of the IGF signaling system, the IGF binding proteins (IGFBPs). Among IGFBP species, IGFBP-3 is the predominant IGF binding protein in human serum. Epidemiological evidence points to a strong correlation between the increased risk of breast and prostate cancer and high IGF-I/low IGFBP-3 levels in circulation, suggesting a potentially protective role for IGFBP-3 in the development of cancer. Numerous in vitro and in vivo studies have shown that IGFBP-3 can induce growth inhibition, apoptosis, and sensitization to therapeutic chemoreagents in breast, prostate, stomach and colon cancer cells. However, the specific biochemical/molecular mechanisms involved in IGFBP-3 action have not been elucidated.

My laboratory has now identified a cell surface receptor protein designated IGFBP-3 receptor (IGFBP-3R) that constitutes a new class of cell-death receptor. This receptor has now been isolated, cloned and expressed, and is presently being investigated as a target for drug development, as well as its own potential therapeutic effects. Specifically, current projects include the biological significance of IGFBP-3/IGFBP-3R axis and the mechanisms involved in its role as a potent apoptotic inducer in human cancer.

Our other major research area focuses on the IGFBP-related proteins (IGFBP-rPs), which are newly identified IGFBP species from my laboratory and appear to be potent anti-proliferative and/or differentiating factors in a variety of human cancers. Awe are currently investigating multiple aspects of the IGFBP-rP1 and -rP2 axes including: (i) identification of signal transduction pathways; (ii) characterization of structure/function aspects of the anti-proliferative and/or differentiating action of IGFBP-rP1 and -rP2; and (iii) adenovirus-mediated gene therapy for breast and lung tumors in animal models.

1. Walker GE; Wilson EM; Powell D; Oh Y; Butyrate, a histone deacetylase inhibitor, activates the human IGFBP-3 promoter in breast cancer cells: Molecular mechanism involves an Sp1/Sp3 multiprotein complex. Endocrinology, 2001, 142:3817-1827.

2. Walker GE; Kim H-S; Yang Y-F; Oh Y. IGF-independent effects of the IGFBP Superfamily. In “Insulin-like Growth Factor” Le Roith D, Zumkeller W, Baxter R, eds, Landes Bioscience, 2002.

3. Kim H-S; Ingermann AR; Tsubaki J; Twigg SM; Oh Y. Cellular expression of insulin-like growth factor binding protein-3 induces apoptosis through the caspase-dependent mechanism in MCF-7 human breast cancer cells. J. Biol. Chem, 2001, in submission.

4. Ingermann AR; Kim H-S; Oh Y. Identification of the IGFBP-3 receptor as a new class of cell-death receptor. Nature medicine, 2001, in preparation.

To contact Dr. Oh directly: ohy@ohsu.edu