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

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.

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

Scientific Reports ◽

10.1038/s41598-018-32711-9 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 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

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Steroid hormone receptors and prostate cancer: role of structural dynamics in therapeutic targeting

Asian Journal of Andrology ◽

10.4103/1008-682x.183380 ◽

2016 ◽

Vol 18 (5) ◽

pp. 682 ◽

Cited By ~ 11

Author(s):

Raj Kumar

Keyword(s):

Prostate Cancer ◽

Structural Dynamics ◽

Hormone Receptors ◽

Steroid Hormone ◽

Steroid Hormone Receptors ◽

Therapeutic Targeting

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

Biochemical Society Transactions ◽

10.1042/bst0341089 ◽

2006 ◽

Vol 34 (6) ◽

pp. 1089-1094 ◽

Cited By ~ 28

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.

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EFFECTS OF EXOGENOUS LACTOFERRIN ON PHENOTYPIC PROFILE AND INVASIVENESS OF HUMAN PROSTATE CANCER CELLS (DU-145 AND LNCaP) IN VITRO

Experimental Oncology ◽

10.31768/2312-8852.2018.40(3):184-189 ◽

2018 ◽

Vol 40 (3) ◽

pp. 184-189 ◽

Cited By ~ 1

Author(s):

T V Zadvornyi ◽

N Yu Lukianova ◽

T V Borikun ◽

V F Chekhun

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Hormone Receptors ◽

Steroid Hormone ◽

Steroid Hormone Receptors ◽

Human Prostate ◽

Human Prostate Cancer ◽

Ki 67 ◽

Phenotypic Profile

Aim: To investigate the biological effects of exogenous lactoferrin (LF) on phenotypic profile and invasiveness of human prostate cancer (PC) cells in vitro. Materials and Methods: Human PC cell lines (LNCaP, DU-145) were cultured with an exogenous LF at a dose corresponding to IC30. The expression levels of steroid hormone receptors (androgen receptor, estrogen receptor, progesterone receptor), Her2/neu, Ki-67, E- and N-cadherin, were monitored by immunohistochemical analysis. The levels of miRNAs were assessed using q-PCR. The invasive activity of the cells was examined in a standard invasion test. Results: Exogenous LF reduced expression of steroid hormone receptors (ERα and PR) and Ki-67 in both PC cell lines. The expression of E-cadherin increased significantly in LF-treated DU-145 cells. Also, we established the decrease in invasive activity upon LF treatment by 40% and 30% in DU-145 and LNCaP cells, respectively. In DU-145 cells, incubation with exogenous LF resulted in an increase in the expression of oncosuppressive (miR-133a and miR-200b) miRNAs. Conclusions: Exogenous LF causes the changes in phenotypic characteristics of PC cells and levels of oncogenic and oncosuppressive miRNAs involved in the regulation of key cellular processes.

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