HER2訊息途徑的活化調控雄性素受體功能與前列腺癌惡化關係之探討
Activation of HER2 Signaling Pathway Modulates AR Functions and Prostate Cancer Progression
Date Issued
2006
Date
2006
Author(s)
Ho, Ping-Chih
DOI
en-US
Abstract
Escaping from androgen ablation therapy makes prostate cancer intractable. The androgen receptor (AR) remains active and supportive to the scenario of PCa development. Deregulations of normal constraints on hormone action activate AR in androgen ablation therapy. Among these deregulation mechanisms, HER2 is considered as one factor providing outlaw pathway to activate AR. HER2 is well studied in breast cancer progression and its tamoxifen resistance, but role of HER2 in prostate cancer progression remains unclear. Here we investigated the molecular basis downstream of HER2 signaling regarding prostate cancer progression. In 22Rv1 reporter cell lines, higher growth rate and colony forming ability correlate with increase of expression and activation level of HER2. We also showed that HER2-specific inhibitor AG825 decreases AR-activated transcription. Analysis on signaling molecules downstream of HER2 for involvement in AR-activated transcription revealed a complete inhibition of AR activity by targeting to PI3K, Rac1, p38α/β and IKKα IKKα. Moreover, inhibitions on these proteins decline the growth rate
and colony forming by inducing apoptosis. On the other hand, increase of p38 levels
and activities correlate with the HER2 expression level. Futhermore,
immnohistological staining in clinical tissue array demonstrated HER2 expression
levels alone with prostatic tumor progression stages. Our data suggest that HER2
overexpression promotes PCa progression might through a PI3K-Rac1-p38α/β-IKKα pathway and is independent of Akt and Erk1/2. This new pathway might
provide possible targets for treating prostate cancer or aid in prevention.
Subjects
雄性素
HER2
PSA
prostate cancer
AR
前列腺癌
SDGs
Type
other
File(s)![Thumbnail Image]()
Loading...
Name
ntu-95-R93b46017-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
(MD5):3b9d63a10fdcf68a1e41c52238208a4c