期刊
ENDOCRINE-RELATED CANCER
卷 20, 期 2, 页码 173-186出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-12-0250
关键词
Castrate-resistant; prostate cancer; IGF2; steroidogenesis; androgen receptor
资金
- Queensland Smart Futures Premier's Fellowship
- Prostate Cancer Foundation of Australia [PCFA PG25]
- Terry Fox Program Project (National Cancer Institute of Canada) [012003, 017007]
- Pfizer
IGF2 is a mitogenic foetal growth factor commonly over-expressed in cancers, including prostate cancer (PC). We recently demonstrated that insulin can activate de novo steroidogenesis in PC cells, a major pathway for reactivation of androgen pathways and PC progression. IGF2 can activate the IGF1 receptor (IGF1R) or insulin receptor (INSR) or hybrids of these two receptors. We therefore hypothesized that IGF2 may contribute to PC progression via de novo steroidogenesis. IGF2 mRNA but not IGF2 receptor mRNA expression was increased in patient samples during progression to castrate-resistant PC as was immunoreactivity to INSR and IGF1R antibodies. Treatment of androgen receptor (AR)-positive PC cell lines LNCaP and 22RV1 with IGF2 for 48 h resulted in increased expression of steroidogenic enzyme mRNA and protein, including steroid acute regulatory protein (StAR), cytochrome p450 family member (CYP) 17A1, aldo-keto reductase family member (AKR) 1C3 and hydroxysteroid dehydrogenase (HSD) 17B3. IGF2 treatment resulted in increased steady state steroid levels and increased de novo steroidogenesis resulting in AR activation as demonstrated by PSA mRNA induction. Inhibition of the IGF1R/INSR signalling axis attenuated the effects of IGF2 on steroid hormone synthesis. We present a potential mechanism for prostatic IGF2 contributing to PC progression by inducing steroidogenesis and that IGF2 signalling and related pathways present attractive targets for PC therapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据