Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β-hydroxysteroid dehydrogenase, 17-20α-hydroxylase, 17β-hydroxysteroid dehydrogenase and 5α-reductase

Glioblastoma (GB) is the most common and aggressive primary brain tumour in adult humans. Therapeutic resistance and tumour recurrence after surgical removal contribute to poor prognosis for glioblastoma patients. Men are known to be more likely than women to develop an aggressive form of GB, and differences in sex steroids have emerged as a leading explanation for this finding. Studies indicate that the metabolism and proliferation of GB-derived cells are increased by sex steroids, the expression of androgen receptors (ARs) and the synthesis of androgens and oestrogens, suggesting that these hormones have a role in the tumour pathogenesis. The expression of aromatase, the enzyme that converts androgens to oestrogens, has been reported in glial cells and GB cell lines. Thus, it was necessary to test whether the steroidogenic enzymes involved in androgen synthesis are expressed in GB cells. Therefore, here, we investigated the expression of four key enzymes involved in androgen synthesis in human-derived GB cells. U87 cells were cultured in Dulbecco's modified Eagle medium plus foetal bovine serum and antibiotics on slides for immunocytochemistry or immunofluorescence. U87, LN229 and C6 cells were also cultured in multi-well chambers to obtain proteins for Western blotting. We used primary antibodies against 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17 alpha-hydroxilase/17,20-lyase (P450c17), 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and 5 alpha-reductase. Immunocytochemistry, and immunofluorescence results revealed that glioblastoma cells express 3 beta-HSD, P450c17, 17 beta-HSD and 5 alpha-reductase proteins in their cytoplasm. Moreover, Western blot analyses revealed bands corresponding to the molecular weight of these four enzymes in the three GB cell lines. Thus, glioblastoma cells have the key enzymatic machinery necessary to synthesize androgens, and these enzymes might be useful targets for new therapeutic approaches.

Automated summary

Glioblastoma cells express key enzymes involved in androgen synthesis, making these enzymes potential targets for new therapeutic approaches. The expression of 3 beta-hydroxysteroid dehydrogenase, P450c17, 17 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase proteins in glioblastoma cells was confirmed through immunocytochemistry, immunofluorescence, and Western blot analyses.