Title

Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer

Authors

Authors

L. D. Robles; A. R. Frost; M. Davila; A. D. Hutson; W. E. Grizzle;R. Chakrabarti

Comments

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Abbreviated Journal Title

J. Biol. Chem.

Keywords

ORIGIN RECOGNITION COMPLEX; DNA-REPLICATION; S-PHASE; MAMMALIAN CDC6; BUDDING YEAST; MCM PROTEINS; EUKARYOTIC CELLS; INITIATION; PHOSPHORYLATION; EXPRESSION; Biochemistry & Molecular Biology

Abstract

CDC6 plays a critical role in regulation of the onset of DNA replication in eukaryotic cells. We have found that Cdc6 expression is down-regulated in prostate cancer as detected by semiquantitative reverse transcriptase-PCR of prostate cell lines and laser-captured microdissected prostate tissues. This result was substantiated by immunohistochemical analysis of paraffin-embedded tissue sections and immunoblot analysis of benign (BPH-1) and adenocarcinomatous prostatic cells. Furthermore, a 100-fold reduction in the transcription efficiency of the Cdc6 promoter-luciferase construct was noted in the metastatic PC3 cells compared with that in BPH-1 cells. Concentration of the E2F and Oct1 transcription factors that have putative binding sites in the Cdc6 promoter was substantially low in PC3 cells compared with BPH cells. Mutagenesis of the two E2F binding sites on the Cdc6 promoter resulted in increased promoter activity in PC3 cells owing to elimination of the negative regulation by pRb-E2F complex but not to the level of that obtained in BPH cells. We conclude that an altered interaction of transcription factors may be responsible for the down-regulation of Cdc6 transcription in PC3 cells. Our study suggests a potential use of the lack of CDC6 expression as an index of prostate cancer development.

Journal Title

Journal of Biological Chemistry

Volume

277

Issue/Number

28

Publication Date

1-1-2002

Document Type

Article

Language

English

First Page

25431

Last Page

25438

WOS Identifier

WOS:000176747000077

ISSN

0021-9258

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