Epigenetic regulation of a novel tumor suppressor gene (hDAB2IP) in prostate cancer cell lines

Hong Chen, Shinichi Toyooka, Adi F. Gazdar, Jer Tsong Hsieh

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

hDAB2IP (human DAB2 (also known as DOC-2) interactive protein) is a novel GTPase-activating protein for modulating the Ras-mediated signal pathway. We demonstrate that the down-regulation of hDAB2IP mRNA in prostate cancer (PCa) cells is regulated by transcriptional levels. Analysis of the hDAB2IP promoter revealed that it is a typical TATA-less promoter containing many GC-rich sequences. In this study, we delineated the potential impact of the epigenetic control of the hDAB2IP promoter on its gene regulation in PCa. Acetylhistone H3 was associated with the hDAB2IP promoter, and CpG islands remained almost unmethylated in normal prostatic epithelia, but not in PCa cell lines. Our data further indicated that trichostatin A (histone deacetylase inhibitor) and 5′-aza-2′-deoxycytidine (DNA hypomethylation agent) acted cooperatively in modulating hDAB2IP gene expression in PCa, whereas histone acetylation played a more significant role in this event. Moreover, a core promoter sequence from the hDAB2IP gene responsible for these treatments was identified. We therefore conclude that epigenetic regulation plays a potential role in regulating hDAB2IP expression in PCa and that these results also provide a new therapeutic strategy for PCa patients.

Original languageEnglish
Pages (from-to)3121-3130
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number5
DOIs
Publication statusPublished - Jan 31 2003
Externally publishedYes

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decitabine
Tumor Suppressor Genes
Epigenomics
Gene expression
Tumors
Prostatic Neoplasms
trichostatin A
Genes
Cells
GC Rich Sequence
GTPase-Activating Proteins
Cell Line
Acetylation
CpG Islands
Histone Deacetylase Inhibitors
Histones
Messenger RNA
DNA
ras GTPase-Activating Proteins
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Epigenetic regulation of a novel tumor suppressor gene (hDAB2IP) in prostate cancer cell lines. / Chen, Hong; Toyooka, Shinichi; Gazdar, Adi F.; Hsieh, Jer Tsong.

In: Journal of Biological Chemistry, Vol. 278, No. 5, 31.01.2003, p. 3121-3130.

Research output: Contribution to journalArticle

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