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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 PublicationsFleming 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. Grill CJ. Cohick WS. Sherman A. (2001) Postnatal development of the rat mammary gland is preserved during iron deficiency. J Nutrition 131:1444-1448 Cohick WS. Wang B. Verma P. Boisclair Y. (2000). Insulin-like growth factor-I and cyclic AMP regulate IGF binding protein-3 gene expression by transcriptional and post-transcriptional mechanisms in mammary epithelial cells. Endocrinology 4583-4591. Grill CJ. Cohick WS. (2000). Insulin-like growth factor binding protein-3 mediates IGF-I action in a bovine mammary epithelial cell line independent of an IGF interaction. J Cellular Physiology 183:273-283. |