scholarly journals Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer

Oncogene ◽  
2008 ◽  
Vol 27 (57) ◽  
pp. 7201-7211 ◽  
Author(s):  
A Rodriguez-Gonzalez ◽  
K Cyrus ◽  
M Salcius ◽  
K Kim ◽  
C M Crews ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Breast And Prostate Cancer

scholarly journals CBP/p300: Critical Co-Activators for Nuclear Steroid Hormone Receptors and Emerging Therapeutic Targets in Prostate and Breast Cancers

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2872
Author(s):  
Aaron R. Waddell ◽  
Haojie Huang ◽  
Daiqing Liao
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Tumor Growth ◽  
Signaling Pathways ◽  
Cell Cycle Progression ◽  
Hormone Receptors ◽  
Steroid Hormone Receptors ◽  
Breast Cancers ◽  
Creb Binding Protein ◽  
Breast And Prostate Cancer

The CREB-binding protein (CBP) and p300 are two paralogous lysine acetyltransferases (KATs) that were discovered in the 1980s–1990s. Since their discovery, CBP/p300 have emerged as important regulatory proteins due to their ability to acetylate histone and non-histone proteins to modulate transcription. Work in the last 20 years has firmly established CBP/p300 as critical regulators for nuclear hormone signaling pathways, which drive tumor growth in several cancer types. Indeed, CBP/p300 are critical co-activators for the androgen receptor (AR) and estrogen receptor (ER) signaling in prostate and breast cancer, respectively. The AR and ER are stimulated by sex hormones and function as transcription factors to regulate genes involved in cell cycle progression, metabolism, and other cellular functions that contribute to oncogenesis. Recent structural studies of the AR/p300 and ER/p300 complexes have provided critical insights into the mechanism by which p300 interacts with and activates AR- and ER-mediated transcription. Breast and prostate cancer rank the first and forth respectively in cancer diagnoses worldwide and effective treatments are urgently needed. Recent efforts have identified specific and potent CBP/p300 inhibitors that target the acetyltransferase activity and the acetytllysine-binding bromodomain (BD) of CBP/p300. These compounds inhibit AR signaling and tumor growth in prostate cancer. CBP/p300 inhibitors may also be applicable for treating breast and other hormone-dependent cancers. Here we provide an in-depth account of the critical roles of CBP/p300 in regulating the AR and ER signaling pathways and discuss the potential of CBP/p300 inhibitors for treating prostate and breast cancer.

Molecular Biology of the Androgen Receptor

2002 ◽  
Vol 20 (13) ◽  
pp. 3001-3015 ◽  
Author(s):  
Edward P. Gelmann
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Ligand Binding ◽  
Dna Sequences ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Three Dimensional ◽  
Intramolecular Interactions ◽  
Steroid Hormone Receptors ◽  
Dimensional Structure

ABSTRACT: Androgen receptor (AR) is a member of the steroid hormone receptor family of molecules. AR primarily is responsible for mediating the physiologic effects of androgens by binding to specific DNA sequences that influence transcription of androgen-responsive genes. The three-dimensional structure of the AR ligand-binding domain has shown it is similar to other steroid hormone receptors and that ligand binding alters the protein conformation to allow binding of coactivator molecules that amplify the hormone signal and mediate transcriptional initiation. However, AR also undergoes intramolecular interactions that regulate its interactions with coactivators and influence its activity. A large number of naturally occurring mutations of the human AR gene have provided important information about AR molecular structure and intermolecular interactions. AR is also a critical mediator of prostate cancer promotion, conferring growth signals to prostate cancer cells throughout the natural history of the disease. Late-stage prostate cancer, unresponsive to hormonal deprivation, sustains AR signaling through a diverse array of molecular strategies. Variations in the AR gene may also confer genetic predisposition to prostate cancer development and severity. Further understanding of AR action and new strategies to interfere with AR signaling hold promise for improving prostate cancer therapy.

scholarly journals Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Thomas Gevaert ◽  
Yves-Rémi Van Eycke ◽  
Thomas Vanden Broeck ◽  
Hein Van Poppel ◽  
Isabelle Salmon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stromal Cell ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Expression Profiles ◽  
Steroid Hormone Receptors ◽  
Cell Markers

The androgen receptor DNA-binding domain determines androgen selectivity of transcriptional response

2006 ◽  
Vol 34 (6) ◽  
pp. 1089-1094 ◽  
Author(s):  
G. Verrijdt ◽  
T. Tanner ◽  
U. Moehren ◽  
L. Callewaert ◽  
A. Haelens ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Dna Binding ◽  
Cellular Response ◽  
Hormone Receptors ◽  
Target Genes ◽  
Steroid Hormone ◽  
Prostate Gland ◽  
Steroid Hormone Receptors ◽  
Binding Motif

The AR (androgen receptor) is a hormone-dependent transcription factor that translates circulating androgen hormone levels into a physiological cellular response by directly regulating the expression of its target genes. It is the key molecule in e.g. the development and maintenance of the male sexual characteristics, spermatocyte production and prostate gland development and growth. It is also a major factor in the onset and maintenance of prostate cancer and a first target for pharmaceutical action against the further proliferation of prostate cancer cells. The AR is a member of the steroid hormone receptors, a group of steroid-inducible transcription factors sharing an identical consensus DNA-binding motif. The problem of how specificity in gene activation is achieved among the different members of this nuclear receptor subfamily is still unclear. In this report, we describe our investigations on how the AR can specifically activate its target genes, while the other steroid hormone receptors do not, despite having the same consensus monomeric DNA-binding motif. In this respect, we describe how the AR interacts with a newly identified class of steroid-response elements to which only the AR and not, for example, the glucocorticoid receptor can bind.

scholarly journals Steroid Hormone Receptors in Prostate Cancer: A Hard Habit to Break?

Cancer Cell ◽  
2009 ◽  
Vol 16 (6) ◽  
pp. 458-462 ◽  
Author(s):  
Gerhardt Attard ◽  
Colin S. Cooper ◽  
Johann S. de Bono
Keyword(s):  
Prostate Cancer ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors
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