Enzymes as modulators in malignant transformation

Area of Science:

• Endocrinology
• Oncology
• Molecular Biology

Background:

• Sex steroids are implicated in breast and prostate cancer development.
• 17beta-hydroxysteroid dehydrogenases (17HSD) enzymes regulate sex steroid hormone activity.
• Altered 17HSD expression may influence intracellular steroid levels and contribute to cancer progression.

Purpose of the Study:

• To investigate the role of 17HSD types 1, 2, and 5 in breast cancer.
• To analyze the prognostic significance of 17HSD expression in breast tumors.
• To study steroid metabolism changes during prostate cancer progression using a cell model.

Main Methods:

• Analysis of 17HSD types 1, 2, and 5 mRNA expression in 794 breast carcinoma specimens.
• Correlation of 17HSD expression with patient survival and clinicopathological features.
• Development of an LNCaP cell model to study androgen and estrogen metabolism during prostate cancer progression.

Main Results:

• 17HSD type 1 and 2 mRNA were found in normal premenopausal breast tissue but not postmenopausal.
• 17HSD type 1, 2, and 5 mRNA were detected in 16%, 25%, and 65% of breast tumors, respectively.
• Expression of 17HSD type 1 and 5 was associated with significantly shorter overall and disease-free survival, and worse prognosis.
• 17HSD type 5 expression was significantly higher in tumors than normal tissue.
• Prostate cancer cell model showed decreased oxidative and increased reductive 17HSD activity during transformation.

Conclusions:

• 17HSD type 1 and 5 expression are significant prognostic markers in breast cancer.
• Altered steroid metabolism, particularly involving 17HSD enzymes, is crucial in cancer progression.
• Targeting 17HSD enzymes may offer therapeutic strategies for breast and prostate cancers.