D-type cyclins complex with the androgen receptor and inhibit its transcriptional transactivation ability

D-type cyclins regulate distinct cellular processes, such as mitotic cell cycle control, differentiation, and transcription. We have previously shown that the D-type cyclins are critical for the androgen-dependent proliferation of prostate cells. Here, we sought to determine whether cyclin D1 direct...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1999-05, Vol.59 (10), p.2297-2301
Main Authors: KNUDSEN, K. E, CAVENEE, W. K, ARDEN, K. C
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell Cycle - genetics
Cell metabolism, cell oxidation
Cell physiology
Cyclin D1 - metabolism
Cyclin D3
Cyclins - metabolism
Feedback
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Neoplastic
Genes, Dominant
Humans
Molecular and cellular biology
Neoplasm Proteins - metabolism
Prostate-Specific Antigen - genetics
Receptors, Androgen - genetics
Receptors, Androgen - metabolism
RNA, Messenger - biosynthesis
Transcriptional Activation
Tumor Cells, Cultured
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Summary:D-type cyclins regulate distinct cellular processes, such as mitotic cell cycle control, differentiation, and transcription. We have previously shown that the D-type cyclins are critical for the androgen-dependent proliferation of prostate cells. Here, we sought to determine whether cyclin D1 directly influences the transactivation potential of the androgen receptor, a transcription factor that strongly influences androgen-dependent proliferation. We found that ligand-mediated transcriptional activation of a physiological target, prostate-specific antigen, by the androgen receptor was inhibited by cyclins D1 and D3. The ability of D-type cyclins to inhibit androgen receptor transactivation was not shared with other cyclins, and cyclin D1 was as effective as dominant negative mutants of the androgen receptor in inhibiting transactivation. This function of cyclin D1 was independent of its role in cell cycle progression and is likely elicited through its ability to form a specific complex with the androgen receptor. These data underscore the various mechanisms through which the androgen receptor is regulated and also point to a negative feedback role for cyclin D1 in controlling androgen-dependent growth.
ISSN:0008-5472
1538-7445