Title

Androgen regulates Cdc6 transcription through interactions between androgen receptor and E2F transcription factor in prostate cancer cells

Authors

Authors

I. Mallik; M. Davila; T. Tapia; B. Schanen;R. Chakrabarti

Comments

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Abbreviated Journal Title

Biochim. Biophys. Acta-Mol. Cell Res.

Keywords

CDC6; transcription regulation; androgen; androgen receptor; E2F; transcription factor; prostate cancer; DNA-REPLICATION; LNCAP CELLS; MAMMALIAN CDC6; RETINOBLASTOMA PROTEIN; IN-VIVO; EXPRESSION; GROWTH; ACTIVATION; BINDING; CYCLE; Biochemistry & Molecular Biology; Cell Biology

Abstract

Androgen receptor plays a critical role in the development and maintenance of cancers in the prostate. Earlier, we have shown that Cdc6, a regulatory protein for initiation of DNA replication, is down regulated in androgen-insensitive prostate cancer cells. In this report, we studied the involvement of androgen, mediated through androgen receptor (AR) in regulation of Cdc6 expression. Our results demonstrated that androgen treatment stimulated Cdc6 expression in xenograft tumors and androgen-sensitive prostate cancer cells. We also showed that androgen treatment stimulated Cdc6 transcription through possible interaction of AR with the ARE sequence in the Cdc6 promoter and that the stimulatory effect of androgen required intact E2F binding sites in the promoter. Androgen treatment differentially altered nuclear availability of E2F1 and E2F3, and increased the amount of hypophosphorylated retinoblastoma protein (pRb) in the nucleus in a time dependent fashion. We further showed that AR interacted with E2F transcription factors in a ligand-independent manner and that ligand-bound AR was less efficient in interacting with E2F proteins. DNA-protein interaction assays indicated that androgen treatment altered binding of E2F1 to the Cdc6 promoter in prostate cancer cells. We conclude that AR regulates Cdc6 transcription through interaction with the Cdc6 promoter, and complex formation with E2F1 and E2F3 in a differential manner. (c) 2008 Elsevier B.V. All rights reserved.

Journal Title

Biochimica Et Biophysica Acta-Molecular Cell Research

Volume

1783

Issue/Number

10

Publication Date

1-1-2008

Document Type

Article

Language

English

First Page

1737

Last Page

1744

WOS Identifier

WOS:000259917200007

ISSN

0167-4889

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