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Steroid receptors are intracellular proteins that, upon association with their cognate ligand, bind to specific DNA sequences and activate transcription. These receptors are particularly important in the growth and development of an organism and in maintaining homeostasis. Research in Dr. Danielsen's laboratory focuses on both the structure-function relationships of these receptors and on their role in the development and progression of cancer. In breast and prostate cancer, new tumors usually require steroid hormones for growth. This has led to the development of anti-hormone therapy for these cancers. However, in advanced disease the tumor loses the requirement for steroid hormones and anti-hormone therapy fails. Dr. Danielsen is studying the mechanisms by which tumors become hormone independent in two ways. First, he is characterizing mutants in the androgen receptor that occur in prostate cancer. Second, he has discovered a unique pathway by which some receptors can be inactivated in transformed cells. This pathway involves the direct interaction of steroid receptors with viral oncogenes and members of the retinoblastoma and p53 tumor suppresser pathways. The hormone binding properties of the steroid receptors are being studied using in vitro mutagenesis and the production of chimeric glucocorticoid-mineralocorticoid and glucocorticoid-androgen receptors. These chimeric receptors have been used to map regions important for specific steroid binding, and regions of the hormone binding domain that are critical for efficient interaction with the transcriptional machinery. The technique has also been used to develop receptors with novel hormone binding properties which may be useful in gene therapy.
View All Medline Articles by Danielsen, M
Chen D, Kohli K, Zhang S, Danielsen M, Stallcup MR (1994)
Phenylalanine-780 near the C-terminus of the mouse glucocorticoid receptor is important for ligand binding affinity andspecificity.
Mol Endocrinol 8 8
Medline
Zhang S, Danielsen M(1995)
Selective effects of 8-Br-cAMP on agonists and antagonists ofthe glucocorticoid receptor.
Endocrine
Danielsen, M(1995)
In: Gametchu, B (eds) Glucocorticoid receptor structure and leukemic cell responses. Landes,Austin,
Zhang S, Liang X, Danielsen M(1995)
8-Br-cAMP does not convert antagonists of the glucocorticoid receptor into agonists.
Rec Prog Hormone Res
Medline
Martin MB, Garcia-Morales P, Solomon HB, Pierce M, Katz D, Zhang S, Danielsen M,Saceda M (1995)
Effects of 12-O-Tetradecanoylphorbol-13-acetate on estrogen receptor activity inMCF-7 cells.
J Biol Chem
Csikos T, Tay J, Danielsen M(1995)
Expression of the Xenopus laevis mineralocorticoid receptor during metamorphosis
Recent Prog Horm Res
Medline
Zhang S, Liang X, Danielsen M (1996)
Role of the C-terminus of the glucocorticoid receptorin hormone binding and agonist/antagonist discrimination.
Molecular Endocrinology
Medline
Danielsen M, Martinez E(1996)
The glucocorticoid receptorresource
Nucleic Acids Res
Medline
Lu J, Danielsen M(1996)
A Stu I polymorphism in the human androgen receptor gene (AR)
Clin Genet
Medline
Martinez E, Moore DD, Keller E, Pearce D, Robinson V, MacDonald PN, Simons SS Jr, Sanchez E, Danielsen M(1997)
The Nuclear Receptor Resource Project
Nucleic Acids Res
Medline
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