The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Distinct Patterns of Dysregulated Expression of Enzymes Involved in Androgen Synthesis and Metabolism in Metastatic Prostate Cancer Tumors
Open accessAbstract
Androgen receptor (AR) signaling persists in castration-resistant prostate carcinomas (CRPC), because of several mechanisms that include increased AR expression and intratumoral androgen metabolism. We investigated the mechanisms underlying aberrant expression of transcripts involved in androgen metabolism in CRPC. We compared gene expression profiles and DNA copy number alteration (CNA) data from 29 normal prostate tissue samples, 127 primary prostate carcinomas (PCa), and 19 metastatic PCas. Steroidogenic enzyme transcripts were evaluated by quantitative reverse transcriptase PCR in PCa cell lines and circulating tumor cells (CTC) from CRPC patients. Metastatic PCas expressed higher transcript levels for AR and several steroidogenic enzymes, including SRD5A1, SRD5A3, and AKR1C3, whereas expression of SRD5A2, CYP3A4, CYP3A5, and CYP3A7 was decreased. This aberrant expression was rarely associated with CNAs. Instead, our data suggest distinct patterns of coordinated aberrant enzyme expression. Inhibition of AR activity by itself stimulated AKR1C3 expression. The aberrant expression of the steroidogenic enzyme transcripts was detected in CTCs from CRPC patients. In conclusion, our findings identify substantial interpatient heterogeneity and distinct patterns of dysregulated expression of enzymes involved in intratumoral androgen metabolism in PCa. These steroidogenic enzymes represent targets for complete suppression of systemic and intratumoral androgen levels, an objective that is supported by the clinical efficacy of the CYP17 inhibitor abiraterone. A comprehensive AR axis–targeting approach via simultaneous, frontline enzymatic blockade, and/or transcriptional repression of several steroidogenic enzymes, in combination with GnRH analogs and potent antiandrogens, would represent a powerful future strategy for PCa management. Cancer Res; 72(23); 6142–52. ©2012 AACR.
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Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
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Self-citationThe Androgen Axis in Recurrent Prostate Cancer
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Evidence of limited contributions for intratumoral steroidogenesis in prostate cancer
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Karantanos, T., Corn, P. G., & Thompson, T. C. (2013) · Oncogene · doi:10.1038/onc.2013.206 · Cited by 866
11-Oxygenated androgens in health and disease
Turcu, A. F., Rege, J., Auchus, R. J., & Rainey, W. E. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0336-x · Cited by 217
Intracrine androgen biosynthesis, metabolism and action revisited
Schiffer, L., Arlt, W., & Storbeck, K.-H. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.08.016 · Cited by 217
Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism
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Metadata
- Authors
- Mitsiades, N., Sung, C. C., Schultz, N., Danila, D. C., He, B., Eedunuri, V. K., Fleisher, M., Sander, C., Sawyers, C. L., & Scher, H. I.
- Venue
- Cancer Research
- Published
- 2012-11-29
- Volume
- 72
- Issue
- 23
- Pages
- 6142-6152
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2153737103
- Cited by
- 197
- References
- 10
- FWCI
- 18.74
- Type
- journal article
- Language
- en
- Open access
- green
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- Mitsiades, N., Sung, C. C., Schultz, N., Danila, D. C., He, B., Eedunuri, V. K., Fleisher, M., Sander, C., Sawyers, C. L., & Scher, H. I. (2012). Distinct Patterns of Dysregulated Expression of Enzymes Involved in Androgen Synthesis and Metabolism in Metastatic Prostate Cancer Tumors. Cancer Research. https://doi.org/10.1158/0008-5472.can-12-1335
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