Androgen receptor co-activators in the regulation of cellular events in prostate cancer.
Summary of "Androgen receptor co-activators in the regulation of cellular events in prostate cancer."
OBJECTIVES:
Androgen receptor (AR) action in benign and malignant tissue is potentiated by a number of co-regulatory proteins that may interact with one or more receptor domains. With improvement of research methodologies, it became possible to detect a number of co-activators whose expression is increased in prostate cancer tissue.
METHODS:
Manuscripts describing prostate cancer-relevant regulation of cellular events by co-activators are selected and summarized.
RESULTS:
AR co-activators may regulate histone modification, proteasomal degradation, chaperones, sumoylation, chromatin remodeling, and cytoskeleton. Some of them (TIF-2) are up-regulated by androgens, whereas the expression of others increases during androgen ablation (p300, CBP, and Tip60). Most co-factors are important for the stimulation of cellular proliferation, although in some cases (ART-27), they act as tumor suppressors and are deleted in prostate cancer tissue. In addition to stimulating AR, some co-activators suppress apoptosis in prostate cancer cells that do not express the AR (p300 and SRC-3). It was recently shown that the inhibition of p300 slows down proliferation, stimulates apoptosis, and inhibits migration and invasion.
CONCLUSIONS:
Co-factors whose down-regulation results in the alterations of multiple cellular functions may be valid targets for novel therapies in advanced prostate cancer.
Affiliation
Experimental Urology, Department of Urology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria, zoran.culig@i-med.ac.at.
Journal Details
This article was published in the following journal.
Name: World journal of urology
ISSN: 1433-8726
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22105110
- DOI: http://dx.doi.org/10.1007/s00345-011-0797-6
Medical and Biotech [MESH] Definitions
Metribolone
A synthetic non-aromatizable androgen and anabolic steroid. It binds strongly to the androgen receptor and has therefore also been used as an affinity label for this receptor in the prostate and in prostatic tumors.
Receptors, Androgen
Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.
Androgen-insensitivity Syndrome
A familial form of PSEUDOHERMAPHRODITISM transmitted as an X-linked recessive trait. These patients have a karyotype of 46,XY with end-organ resistance to androgen due to mutations in the androgen receptor (RECEPTORS, ANDROGEN) gene. Severity of the defect in receptor quantity or quality correlates with their phenotypes. In these genetic males, the phenotypic spectrum ranges from those with normal female external genitalia, through those with genital ambiguity as in Reifenstein Syndrome, to that of a normal male with INFERTILITY.
Nuclear Receptor Subfamily 2, Group C, Member 1
A DNA-binding orphan nuclear receptor that has specificity for directly repeated (DR) AGGTCA sequences. It binds DNA as either as a homodimer or as a heterodimer with the closely-related orphan nuclear receptor NUCLEAR RECEPTOR SUBFAMILY 2, GROUP C, MEMBER 2. The protein was originally identified as a PROSTATE-specific protein and is involved in the regulation of variety of cellular processes, including CELL DIFFERENTIATION; CELL PROLIFERATION; and APOPTOSIS.
Prostate-specific Antigen
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
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