Human prostate stromal cells stimulate increased PSA production in DHEA-treated prostate cancer epithelial cells
Language: 
English
Abstract: 

Dehydroepiandrosterone (DHEA) is commonly used as a dietary supplement and may affect prostate pathophysiology when metabolized to androgens and/or estrogens. Human prostate LAPC-4 cancer cells with a wild type androgen receptor (AR) were treated with DHEA, androgens dihydrotestosterone (DHT), T, or R1881), and E2 and assayed for prostate specific antigen (PSA) protein and gene expression. In LAPC-4 monocultures, DHEA and E2 induced little or no increase in PSA protein or mRNA expression compared to androgen-treated cells. When prostate cancer-associated (6S) stromal cells were added in coculture, DHEA stimulated LAPC-4 cell PSA protein secretion to levels approaching induction by DHT. Also, DHEA induced 15-fold more PSA mRNA in LAPC-4 cocultures than in monocultures. LAPC-4 proliferation was increased 2-3-fold when cocultured with 6S stromal cells regardless of hormone treatment. DHEA-treated 6S stromal cells exhibited a dose- and time-dependent increase in T secretion, demonstrating stromal cell metabolism of DHEA to T. Coculture with non-cancerous stroma did not induce LAPC-4 PSA production, suggesting a differential modulation of DHEA effect in a cancer-associated prostate stromal environment. This coculture model provides a research approach to reveal detailed endocrine, intracrine, and paracrine signaling between stromal and epithelial cells that regulate tissue homeostasis within the prostate, and the role of the tumor microenvironment in cancer progression.

Author(s): 
Arnold, Julia T.
Gray, Nora E.
Jacobowitz, Ketzela
Viswanathan, Lavanya
Cheung, Pui W.
McFann, Kimberly K.
Le, Hanh
Blackman, Marc R.
Item Type: 
Journal Article
Publication Title: 
The Journal of Steroid Biochemistry and Molecular Biology
Journal Abbreviation: 
J. Steroid Biochem. Mol. Biol.
Publication Date: 
Sep 2008
Publication Year: 
2008
Pages: 
240-246
Volume: 
111
Issue: 
3-5
ISSN: 
0960-0760
DOI: 
10.1016/j.jsbmb.2008.06.008
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 18621129 PMCID: PMC2570207

Turabian/Chicago Citation

Julia T. Arnold, Nora E. Gray, Ketzela Jacobowitz, Lavanya Viswanathan, Pui W. Cheung, Kimberly K. McFann, Hanh Le and Marc R. Blackman. Sep 2008. "Human prostate stromal cells stimulate increased PSA production in DHEA-treated prostate cancer epithelial cells." The Journal of Steroid Biochemistry and Molecular Biology 111: 3-5: 240-246. 10.1016/j.jsbmb.2008.06.008.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.jsbmb.2008.06.008 | issn = 0960-0760 | volume = 111 | pages = 240-246 | last = Arnold | first = Julia T. | coauthors = Gray, Nora E., Jacobowitz, Ketzela, Viswanathan, Lavanya, Cheung, Pui W., McFann, Kimberly K., Le, Hanh, Blackman, Marc R. | title = Human prostate stromal cells stimulate increased PSA production in DHEA-treated prostate cancer epithelial cells | journal = The Journal of Steroid Biochemistry and Molecular Biology | date = Sep 2008 | pmid = | pmc = }} </ref>