Dr. Gregory Brent's laboratory focuses on understanding gene regulation by nuclear acting hormones, especially thyroid hormone (T3) and retinoic acid (RA), which combine with nuclear receptors (RAR and TR). He studies the regulation and co-regulation of genes by T3 and RA as influenced by the DNA response element(s), the specific TR and RAR receptor isoforms available, nuclear receptor partners, ligand(s) concentration, and response co-activators and co-repressors. He studies T3 and RA influences on metabolism and gene regulation in hormone-dependent cancer. The sodium/iodide symporter (NIS) gene is normally expressed in the thyroid and the lactating breast. Brent has studied factors associated with reduced expression of NIS in thyroid cancer and approaches to augment NIS expression in breast cancer. He has identified RA regulation of the NIS gene in breast cancer cell lines and in vivo models through modification of signal transduction pathways. He has studied in vitro and in vivo models to promote radioiodine uptake into breast cancer after systemic treatment with retinoids. He is currently mapping signal transduction pathways in thyroid and breast cancer modified by RA treatment, with the goal of improving radioiodine therapy.
Selected Cancer-Related Publications:
Ohashi E, Kogai T, Kagechika H, Brent GA. Activation of the PI3 kinase pathway by retinoic acid mediates sodium/iodide symporter induction and iodide transport in MCF-7 breast cancer cells. Cancer Res. 2009 Apr 15;69(8):3443-50. Epub 2009 Apr 7.
Kogai T, Ohashi E, Jacobs MS, Sajid-Crockett S, Fisher ML, Kanamoto Y, Brent GA. Retinoic acid stimulation of the sodium/iodide symporter in MCF-7 breast cancer cells is mediated by the insulin growth factor-I/phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase signaling pathways. J Clin Endocrinol Metab. 2008 May;93(5):1884-92. Epub 2008 Mar 4.
Kogai T, Sajid-Crockett S, Newmarch LS, Liu YY, Brent GA. Phosphoinositide-3-kinase inhibition induces sodium/iodide symporter expression in rat thyroid cells and human papillary thyroid cancer cells. J Endocrinol. 2008 Nov;199(2):243-52. Epub 2008 Sep 1.
Kogai T, Kanamoto Y, Li AI, Che LH, Ohashi E, Taki K, Chandraratna RA, Saito T, Brent GA. Differential regulation of sodium/iodide symporter gene expression by nuclear receptor ligands in MCF-7 breast cancer cells. Endocrinology. 2005 Jul;146(7):3059-69. Epub 2005 Apr 7.
Kogai T, Kanamoto Y, Che LH, Taki K, Moatamed F, Schultz JJ, Brent GA. Systemic retinoic acid treatment induces sodium/iodide symporter expression and radioiodide uptake in mouse breast cancer models. Cancer Res. 2004 Jan 1;64(1):415-22.