Coordinated Androgen Biosynthesis in Prostate Cancer Tissue

Researchers at Kanazawa University have identified a previously unknown mechanism through which advanced prostate cancer (PCa) often relapses after androgen deprivation therapy (ADT). The study, published in Endocrine-related Cancer, reveals that prostate stromal cells and androgen-sensitive PCa LNCaP cells coordinately activate the androgen receptor through the synthesis of testosterone and dihydrotestosterone from dehydroepiandrosterone (DHEA). This coordinated action of stromal cells and LNCaP cells stimulates the proliferation of LNCaP cells under physiological concentrations of DHEA.

Key Takeaways:

• Prostate stromal cells increase DHEA-induced PSA promoter activity via androgen receptor activation in androgen-sensitive PCa LNCaP cells.
• The addition of prostate stromal cells or PCa-derived stromal cells (PCaSC) to LNCaP cells increases DHEA-induced PSA promoter activity and stimulates the proliferation of LNCaP cells.
• Biosynthesis of testosterone or dihydrotestosterone from DHEA in stromal cells and LNCaP cells is involved in the stimulation of LNCaP cell proliferation.
• Androgen biosynthesis from DHEA depends on the activity of various steroidogenic enzymes present in stromal cells.
• The dual 5alpha-reductase inhibitor dutasteride appears to function not only as a 5alpha-reductase inhibitor but also as a 3beta-hydroxysteroid dehydrogenase inhibitor in LNCaP cells.
• This coculture assay system provides new insights into coordinate androgen biosynthesis under the microenvironment of PCa cells before and after ADT.

Statistics:

• 1139-55: Page numbers of the study published in Endocrine-related Cancer.
• 16(4): Volume and issue number where the study was published in Endocrine-related Cancer.

Sources:

• Mizokami, A., et al. "Prostate cancer stromal cells and LNCaP cells coordinately activate the androgen receptor through synthesis of testosterone and dihydrotestosterone from dehydroepiandrosterone." Endocrine-related Cancer, vol. 16, no. 4, 2009, pp. 1139-55.
• Kanazawa University Graduate School of Medical Sciences, Dept. of Integrative Cancer Therapy and Urology
• Springer, 233 Spring Street, New York, NY 10013, USA.