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Cell biology (growth factors. signal transduction. mammary gland biology)Research in my laboratory focuses on the role of the insulin-like growth factors (IGF) in mammary gland growth and development. A specific focus is to understand the molecular and cellular mechanisms by which these growth factors regulate growth. differentiation and cell survival of mammary epithelial cells. This cell type is responsible for milk synthesis and is also a common site of origin of mammary carcinoma. The IGFs associate with a family of high-affinity binding proteins (IGFBP) which modulate their biological activity. For example we have found that IGF-I specifically stimulates the synthesis of IGF binding protein-3 by mammary epithelial cells. When these cells are transfected to overexpress this protein. they exhibit enhanced responsiveness to IGF-I in terms of DNA synthesis. We are currently investigating the mechanisms underlying this observation. Specific areas of research include:
Selected PublicationsJetzt AE, Cheng JS, Tumer NE, Cohick WS. (2009) Ricin A-chain requires c-Jun N-terminal kinase to induce apoptosis in nontransformed epithelial cells. Int J Biochem Cell Biol. 41(12):2503-10. Leibowitz BJ, Cohick WS. (2009) Endogenous IGFBP-3 is required for both growth factor-stimulated cell proliferation and cytokine-induced apoptosis in mammary epithelial cells. J Cell Physiol. 220(1):182-8. Fleming JM, Brandimarto JA, Cohick WS. (2007) The mitogen-activated protein kinase pathway tonically inhibits both basal and IGF-I-stimulated IGF-binding protein-5 production in mammary epithelial cells. J Endocrinol. 194(2):349-59. Fleming JM, Desury G, Polanco TA, Cohick WS. (2006) Insulin growth factor-I and epidermal growth factor receptors recruit distinct upstream signaling molecules to enhance AKT activation in mammary epithelial cells. Endocrinology. 147(12):6027-35. Sivaprasad U. Fleming J. Verma PS. Hogan KA. Desury G. Cohick WS. (2004) Stimulation of insulin-like growth factor (IGF) binding protein-3 synthesis by IGF-I and transforming growth factor-α is mediated by both phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways in mammary epithelial cells. Endocrinology 145:4213-4221. Cornwell T. Cohick WS. Raskin I. (2004) Dietary phytoestrogens and health. Phytochemistry 65:995-1016. Grill CJ. Sivaprasad U. Cohick WS. (2002) Constitutive expression of IGF binding protein-3 by mammary epithelial cells alters signaling through akt and p70S6 kinase. J Mol Endocrinol 29:153-162. |