Begell House Inc.
Critical Reviews™ in Eukaryotic Gene Expression
CRE
1045-4403
5
2
1995
Androgen Receptor: An Overview
97-125
10.1615/CritRevEukarGeneExpr.v5.i2.10
Chawnshang
Chang
Department of Human Oncology and Program in Endocrinology-Reproductive Physiology, University of Wisconsin, Madison, Wisconsin 53792
Alan
Saltzman
Department of Human Oncology and Program in Endocrinology-Reproductive Physiology, University of Wisconsin, Madison, Wisconsin 53792
Shuyuan
Yeh
Department of Human Oncology and Program in Endocrinology-Reproductive Physiology, University of Wisconsin, Madison, Wisconsin 53792
Winjing
Young
Department of Human Oncology and Program in Endocrinology-Reproductive Physiology, University of Wisconsin, Madison, Wisconsin 53792
Evan T.
Keller
Department of Urology, School of Medicine, University of Michigan, 1500 E. Medical Center Dr., Room 5308 CCGCB, Ann Arbor, MI 48105, USA; Center for Translational Medicine, Guangxi Medical University, Nanning, China
Han-Jung
Lee
Department of Human Oncology and Program in Endocrinology-Reproductive Physiology, University of Wisconsin, Madison, Wisconsin 53792
Chihuei
Wang
Department of Human Oncology and Program in Endocrinology-Reproductive Physiology, University of Wisconsin, Madison, Wisconsin 53792
Atsushi
Mizokami
Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan
androgen receptor
prostate
Tfm
testosterone.
The action of androgens in regulating development and growth is mediated by androgen receptor (AR). AR is a member of the steroid hormone receptor superfamily, a class of receptors that function through their ability to regulate the transcription of specific genes. The AR is located in various target tissues, with its levels and activity altered with the onset of various cellular events (e.g., sexual development, malignant transformation). The modulation of AR levels occurs through a number of mechanisms, including transcription, and is regulated by various factors (e.g., androgens). The ability of AR to modulate gene transcription is through its interaction with specific DNA sequences located near or within the target gene promoter. The importance of the AR in reproductive physiology has been emphasized by the finding of AR mutations, leading to a variety of disorders, including testicular feminization syndrome. In this article, we review the structure and function of AR and the role AR plays in the function of the mammalian system.
Cyclins, Cyclin-Dependent Kinases and Cdk Inhibitors: Implications in Cell Cycle Control and Cancer
127-156
10.1615/CritRevEukarGeneExpr.v5.i2.20
Timothy K.
MacLachlan
Jefferson Cancer Institute, Departments of Microbiology/Immunology and Pathology, Thomas Jefferson University, Philadelphia, PA 19107
Nianli
Sang
Department of Biology, College of Arts and Sciences, Drexel University; Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania
Antonio
Giordano
Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, Philadelphia, PA 19107
cell division cycle
cyclins
cyclin-dependent kinases
CDK inhibitors
oncogenesis.
A significant portion of cellular scientific literature published is dedicated to describing the cloning, the link to cancer, or the characterization of proteins involved in the progression of the cell cycle. With this abundance of information, the cascading pathways of molecular events that occur in the cell cycle are proving to be exceedingly complicated. Originally, the sole regulator of the fission yeast cell division cycle, cdc2, was thought to also regulate mammalian cell cycles in the same manner. However, mammalian cdc2 has now been joined by seven well-characterized relatives acting at distinct points in the cell cycle. These kinases are activated by larger proteins called cyclins, named with respect to their cyclical expression and degradation. Therefore, the catalytic subunits of these complexes are named cyclin-dependent kinases (cdks). In the event that the cell must stop normal cycling behavior, a number of cdk inhibitors, which have only begun to be characterized, function in inhibiting the kinase ability of cdks, among other nonproliferative acts. The external environment manipulates cellular proliferation and differentiation by stimulating or inhibiting certain signal transduction pathways. However, each component of the cell cycle machinery, as they are the final executors in cell division, has the potential to elicit or to contribute to a neoplastic phenotype. This review focuses on the characterization of each member of the cell cycle protein family and also addresses the potential role each plays in cancer.
Androgen Action
157-176
10.1615/CritRevEukarGeneExpr.v5.i2.30
Arun K.
Roy
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284
Bandana
Chatterjee
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284
testosterone
steroid hormone
androgen receptor
transacting factor
androgen-insensitivity syndrome.
Androgens are C-19 steroids that provide major regulatory influences on male reproductive function. Testosterone, the principal androgenic steroid, is secreted by the Leydig cells of the testes. Both testosterone and its 5α reduced derivative 5α-dihydrotestosterone (DHT) are physiological ligands for the androgen receptor (AR). Ligand-activated AR acts as a nuclear transcription factor and mediates androgen action. AR, along with receptors for a number of C-21 steroids such as glucocorticoid, mineralocorticoid, and progesterone, share the same 15 base pair consensus element composed of 5’-GGA/TACAnnnTGTTCT-3’. Despite this cross-reactivity at the level of the DNA, physiologically, androgens regulate their target genes with a high degree of receptor specificity. Such a regulatory specificity appears to be due to multiphasic interactions involving enzymatic activation/inactivation of the steroid ligand, interaction with specific receptor-associated nuclear factors on or around the hormone response element, and differential regulation of the receptor gene expression. Conversion of testosterone to 5α-dihydrotestosterone in target cells is a widespread activation mechanism that amplifies the androgenic signal. Unlike the testosterone-AR complex, DHT-activated AR has a longer half-life, and thus prolongs androgen action. Oxido-reduction of androgens by 17β-hydroxysteroid dehydrogenase and sulfurylation by androgen sulfotransferase are two major pathways of androgen inactivation in target cells. Prenatal deprivation of androgen action, due to mutations in either the AR or the 5α-reductase gene, results in developmental abnormalities of male reproductive tissues and also cause partial or complete androgen-insensitivity syndromes. Elucidation of various molecular steps in androgen action is allowing development of improved therapeutic agents for the management of disorders of androgen action such as the prostatic hypertrophy and neoplasia.
Biophysical Modulation of Cell and Tissue Structure and Function
177-191
10.1615/CritRevEukarGeneExpr.v5.i2.40
Janet
Rubin
Department of Medicine, Veterans Administration Hospital, Emory University School of Medicine, Decatur, Georgia
Clinton T.
Rubin
Department of Medicine, Veterans Administration Hospital, Emory University School of Medicine, Decatur, Georgia
Kenneth J.
McLeod
Musculo-Skeletal Research Laboratory, Department of Orthopaedics, State University of New York, Stony Brook, New York