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 language | English |
|---|---|
| Pages (from-to) | 3121-3130 |
| Number of pages | 10 |
| Journal | Journal of Biological Chemistry |
| Volume | 278 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jan 31 2003 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Epigenetic regulation of a novel tumor suppressor gene (hDAB2IP) in prostate cancer cell lines
AU - Chen, Hong
AU - Toyooka, Shinichi
AU - Gazdar, Adi F.
AU - Hsieh, Jer Tsong
PY - 2003/1/31
Y1 - 2003/1/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037474235&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037474235&partnerID=8YFLogxK
U2 - 10.1074/jbc.M208230200
DO - 10.1074/jbc.M208230200
M3 - Article
C2 - 12446720
AN - SCOPUS:0037474235
VL - 278
SP - 3121
EP - 3130
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 5
ER -