Document Detail


IGF2 increases de novo steroidogenesis in prostate cancer cells.
MedLine Citation:
PMID:  23319492     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Amy A Lubik; Jennifer H Gunter; Brett G Hollier; Susan Ettinger; Ladan Fazli; Nataly Stylianou; Stephen C Hendy; Hans H Adomat; Martin E Gleave; Michael Pollak; Adrian Herington; Colleen C Nelson
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-22
Journal Detail:
Title:  Endocrine-related cancer     Volume:  20     ISSN:  1479-6821     ISO Abbreviation:  Endocr. Relat. Cancer     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-25     Completed Date:  2013-09-13     Revised Date:  2013-10-07    
Medline Journal Info:
Nlm Unique ID:  9436481     Medline TA:  Endocr Relat Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  173-86     Citation Subset:  IM    
Affiliation:
Institute of Health and Biomedical Innovation, Australian Prostate Cancer Research Centre - Queensland, Princess Alexandra Hospital, Queensland University of Technology, Level 1, Building 1, 199 Ipswich Road, Brisbane, Queensland 4102, Australia.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Humans
Insulin-Like Growth Factor II / genetics,  pharmacology*
Male
Prostate-Specific Antigen / genetics
Prostatic Neoplasms / metabolism*
RNA, Messenger / metabolism
Receptor, IGF Type 2 / genetics
Steroids / biosynthesis*
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Receptor, IGF Type 2; 0/Steroids; 67763-97-7/Insulin-Like Growth Factor II; EC 3.4.21.77/Prostate-Specific Antigen
Comments/Corrections
Comment In:
Endocr Relat Cancer. 2013;20(5):C19-21   [PMID:  23818573 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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