Gregory A. Brent

Laboratory Address:
West LA VA Bldg 114
Los Angeles, CA 90095

Work Address:
West LA VA Bldg 114
Los Angeles, CA 90095

Affiliations
Affiliations
Interim Chief, Endocrinology, Diabetes and Hypertension
Professor, Medicine
Member, Molecular, Cell, and Developmental Biology, JCCC Signal Transduction and Therapeutics Program Area, Molecular, Cellular & Integrative Physiology GPB Home Area
Research Interests
My laboratory is focused on understanding gene regulation by nuclear acting hormones, especially thyroid hormone (T3) and retinoic acid (RA). RA and T3 have a wide range of actions including effects on neural development, hematologic stem cell maturation, tumor cell growth, metabolism and pituitary function. RA and T3 regulate gene expression by combining with nuclear receptors (RAR and TR) which bind to regulatory regions of specific genes. We study 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. There are two T3 receptor (TR) genes, and various TR isoforms that are differentially expressed developmentally and in adult tissues. We have used gene targeting techniques and pharmacological approaches to map TR isoform-specific actions. We are using both in vivo studies as well as in vitro embryonic stem cell differentiation models. We have identified TR isoform specific actions in neural differentiation, adaptive thermogenesis, and in bone development. The sodium/iodide symporter (NIS) gene is normally expressed in the thyroid and the lactating breast. We have studied factors associated with reduced expression in thyroid cancer. We have identified RA regulation of the sodium/iodide symporter gene in breast cancer cell lines by modification of signal transduction pathways. We are studying in vitro and in vivo models to promote radioiodine uptake into breast cancer by treatment with retinoids. This approach has potential application for the diagnosis and treatment of breast cancer.
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 research 2009; 69(8): 3443-50.
Kogai Takahiko, Ohashi Emi, Jacobs Megan S, Sajid-Crockett Saima, Fisher Myrna L, Kanamoto Yoko, Brent Gregory A 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. The Journal of clinical endocrinology and metabolism. 2008; 93(5): 1884-92.
Liu Yan-Yun, Heymann Robert S, Moatamed Farhad, Schultz James J, Sobel Daniel, Brent Gregory A A mutant thyroid hormone receptor alpha antagonizes peroxisome proliferator-activated receptor alpha signaling in vivo and impairs fatty acid oxidation. Endocrinology. 2007; 148(3): 1206-17.
Kogai Takahiko, Kanamoto Yoko, Li Andrew I, Che Lisa H, Ohashi Emi, Taki Katsumi, Chandraratna Roshantha A, Saito Tsukasa, Brent Gregory A Differential regulation of sodium/iodide symporter gene expression by nuclear receptor ligands in MCF-7 breast cancer cells. Endocrinology. 2005; 146(7): 3059-69.
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 research. . 2004; 64(1): 415-22.
Liu, YY Schultz, JJ Brent, GA A thyroid hormone receptor alpha gene mutation (P398H) is associated with visceral adiposity and impaired catecholamine-stimulated lipolysis in mice. The Journal of biological chemistry. . 2003; 278(40): 38913-20.
Liu Yan-Yun, Tachiki Ken H, Brent Gregory A A targeted thyroid hormone receptor alpha gene dominant-negative mutation (P398H) selectively impairs gene expression in differentiated embryonic stem cells. Endocrinology. 2002; 143(7): 2664-72.
Kogai T, Schultz J, Johnson L, Huang M, Brent GA Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line. Proceeding of the National Academy of Sciences (USA) 2000; 97: 8519-8524.