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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 di...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502219/ https://www.ncbi.nlm.nih.gov/pubmed/34505421 http://dx.doi.org/10.1002/edm2.289 |
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author | Mondragón, Jose Antonio Serrano, Yesenia Torres, Andrea Orozco, Martin Segovia, Jose Manjarrez, Gabriel Romano, Marta Catalina |
author_facet | Mondragón, Jose Antonio Serrano, Yesenia Torres, Andrea Orozco, Martin Segovia, Jose Manjarrez, Gabriel Romano, Marta Catalina |
author_sort | Mondragón, Jose Antonio |
collection | PubMed |
description | 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 3β‐hydroxysteroid dehydrogenase (3β‐HSD), 17α‐hydroxilase/17,20‐lyase (P450c17), 17β‐hydroxysteroid dehydrogenase (17β‐HSD) and 5α‐reductase. Immunocytochemistry, and immunofluorescence results revealed that glioblastoma cells express 3β‐HSD, P450c17, 17β‐HSD and 5α‐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. |
format | Online Article Text |
id | pubmed-8502219 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85022192021-10-14 Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase Mondragón, Jose Antonio Serrano, Yesenia Torres, Andrea Orozco, Martin Segovia, Jose Manjarrez, Gabriel Romano, Marta Catalina Endocrinol Diabetes Metab Original Research Articles 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 3β‐hydroxysteroid dehydrogenase (3β‐HSD), 17α‐hydroxilase/17,20‐lyase (P450c17), 17β‐hydroxysteroid dehydrogenase (17β‐HSD) and 5α‐reductase. Immunocytochemistry, and immunofluorescence results revealed that glioblastoma cells express 3β‐HSD, P450c17, 17β‐HSD and 5α‐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. John Wiley and Sons Inc. 2021-07-23 /pmc/articles/PMC8502219/ /pubmed/34505421 http://dx.doi.org/10.1002/edm2.289 Text en © 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Articles Mondragón, Jose Antonio Serrano, Yesenia Torres, Andrea Orozco, Martin Segovia, Jose Manjarrez, Gabriel Romano, Marta Catalina Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase |
title | Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase |
title_full | Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase |
title_fullStr | Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase |
title_full_unstemmed | Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase |
title_short | Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase |
title_sort | glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β‐hydroxysteroid dehydrogenase, 17‐20α‐hydroxylase, 17β‐hydroxysteroid dehydrogenase and 5α‐reductase |
topic | Original Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502219/ https://www.ncbi.nlm.nih.gov/pubmed/34505421 http://dx.doi.org/10.1002/edm2.289 |
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