Our results systematically present the regulation of steroid-converting enzymes and their roles in modulating the intratumoral steroid-hormone levels in BC with a vivid 3D-schema, supporting novel therapy targeting the reductive 17β-HSD7 and proposing a new combined therapy targeting 11β-HSD2 and 17β-HSD7.
The HSD11B2 promoter was subcloned and luciferase reporter assays evaluated GR-dependent HSD11B2 regulation, and 11β-HSD2 expression/activity was studied in human breast cancer MCF7 cells, endogenously expressing this enzyme.
Reductive 17β-hydroxysteroid dehydrogenases (17β-HSDs) and 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) play crucial roles in respectively regulating steroids and glucocorticoids for the progression of hormone-dependent breast cancer.
The analysis of several human BC mRNA databases indicated that 11βHSD2 and ChEH overexpression correlated with a higher risk of patient death, highlighting that the biosynthetic pathway producing OCDO is of major importance to BC pathology.
In conclusion, genetic variants of 17β-HSD2 and 17β-HSD7 may affect intra-tumour gene expression as well as breast cancer E2 levels in postmenopausal women.
To verify the relevance of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in controlling breast-cancer cell growth, we have evaluated the correlation of 11beta-HSD2 expression and antiproliferative effects of glucocorticosteroids (GCs) on breast cancer cell proliferation.