Back to Search
Start Over
Insulin increases de novo steroidogenesis in prostate cancer cells.
- Source :
-
Cancer research [Cancer Res] 2011 Sep 01; Vol. 71 (17), pp. 5754-64. Date of Electronic Publication: 2011 Jul 11. - Publication Year :
- 2011
-
Abstract
- Androgen-dependent pathways regulate maintenance and growth of normal and malignant prostate tissues. Androgen deprivation therapy (ADT) exploits this dependence and is used to treat metastatic prostate cancer; however, regression initially seen with ADT gives way to development of incurable castration-resistant prostate cancer (CRPC). Although ADT generates a therapeutic response, it is also associated with a pattern of metabolic alterations consistent with metabolic syndrome including elevated circulating insulin. Because CRPC cells are capable of synthesizing androgens de novo, we hypothesized that insulin may also influence steroidogenesis in CRPC. In this study, we examined this hypothesis by evaluating the effect of insulin on steroid synthesis in prostate cancer cell lines. Treatment with 10 nmol/L insulin increased mRNA and protein expression of steroidogenesis enzymes and upregulated the insulin receptor substrate insulin receptor substrate 2 (IRS-2). Similarly, insulin treatment upregulated intracellular testosterone levels and secreted androgens, with the concentrations of steroids observed similar to the levels reported in prostate cancer patients. With similar potency to dihydrotestosterone, insulin treatment resulted in increased mRNA expression of prostate-specific antigen. CRPC progression also correlated with increased expression of IRS-2 and insulin receptor in vivo. Taken together, our findings support the hypothesis that the elevated insulin levels associated with therapeutic castration may exacerbate progression of prostate cancer to incurable CRPC in part by enhancing steroidogenesis.<br /> (©2011 AACR.)
- Subjects :
- Alcohol Oxidoreductases biosynthesis
Alcohol Oxidoreductases genetics
Androgens biosynthesis
Animals
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Humans
Insulin pharmacology
Insulin Receptor Substrate Proteins biosynthesis
Insulin Receptor Substrate Proteins genetics
Male
Mice
Prostate-Specific Antigen biosynthesis
Prostate-Specific Antigen genetics
Prostatic Neoplasms enzymology
Protein Biosynthesis drug effects
Protein Biosynthesis genetics
RNA, Messenger biosynthesis
Xenograft Model Antitumor Assays
Gonadal Steroid Hormones biosynthesis
Insulin physiology
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 71
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 21747118
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-10-2470