17 beta-hydroxysteroid dehydrogenases and cancers

Area of Science:

• Steroid hormone metabolism
• Enzymology
• Cancer biology

Background:

• 17 beta-Hydroxysteroid dehydrogenases (17HSDs) interconvert active 17 beta-hydroxysteroids and 17-ketosteroids, influencing estrogen and androgen availability.
• Estrogens are implicated in breast cancer etiology, while androgens affect prostate cell growth.
• 17HSDs exhibit distinct enzymatic properties and tissue-specific expression, suggesting diverse physiological roles.

Purpose of the Study:

• To investigate changes in androgen and estrogen metabolism during prostate cancer progression using a cell model.
• To explore the differential expression and activity of 17HSD isoenzymes in breast and colon cancer.
• To assess the potential of targeting 17HSDs for cancer therapy.

Main Methods:

• Development of a cell model using LNCaP prostate cancer cells to study transformation to more aggressive phenotypes.
• Analysis of androgen and estrogen metabolism in cultured LNCaP cells during transformation.
• Examination of 17HSD type 1 and type 2 expression and activity in breast and colon cancer cell lines and tissues.

Main Results:

• Prostate cancer cell transformation in culture is associated with significant alterations in sex hormone metabolism, including increased estrogen production.
• 17HSD type 1 activity appears prevalent in malignant breast cells, whereas 17HSD type 2 predominates in normal breast cells.
• 17HSD type 2 expression is significantly reduced in colon cancer compared to normal colonic mucosa.

Conclusions:

• Alterations in 17HSD activity and expression are crucial in the development and progression of hormone-related cancers.
• Targeting 17HSD type 1 may offer a therapeutic strategy for estrogen-dependent breast cancer.
• Estrogen metabolism, influenced by 17HSDs, plays a role in non-traditional target tissues like the colon.