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Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer

We sought to evaluate androgen receptor (AR) and PI3K pathway activity in ovarian cancer cell lines and tissue and determine if either pathway was correlated with growth of ovarian cancers. AR expression and activity were quantified using immunohistochemistry (IHC) and RT-qPCR in six ovarian cancer...

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Autores principales: Hill, Addie, Cristea, Mihaela, He, Miaoling, Frankel, Paul, Neuhausen, Susan, Pal, Sumanta K, Jones, Jeremy O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682960/
https://www.ncbi.nlm.nih.gov/pubmed/34926721
http://dx.doi.org/10.17303/jcrto.2019.7.103
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author Hill, Addie
Cristea, Mihaela
He, Miaoling
Frankel, Paul
Neuhausen, Susan
Pal, Sumanta K
Jones, Jeremy O
author_facet Hill, Addie
Cristea, Mihaela
He, Miaoling
Frankel, Paul
Neuhausen, Susan
Pal, Sumanta K
Jones, Jeremy O
author_sort Hill, Addie
collection PubMed
description We sought to evaluate androgen receptor (AR) and PI3K pathway activity in ovarian cancer cell lines and tissue and determine if either pathway was correlated with growth of ovarian cancers. AR expression and activity were quantified using immunohistochemistry (IHC) and RT-qPCR in six ovarian cancer cell lines and 51 tissue samples. Phospho-mTOR and AKT expression were quantified by IHC as well. Cell growth was assessed in the presence of AR modulating drugs and metformin. We found that despite robust AR expression and activity, no cell line was dependent on androgen for growth. However, metformin inhibited activity in five of the six cell lines. Patient tissues had large variation in AR expression and activity, as well as in expression of phospho-mTOR and AKT, but none of these variables correlated with progression-free survival (PFS). AR expression and activity did not predict the dependence of ovarian cancer cell lines on androgens for growth, and AR expression and activity did not correlate with PFS. This result suggests that AR expression as a criterion for patient selection for clinical trials evaluating molecules targeting AR may not predict response for ovarian cancer patients.
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spelling pubmed-86829602021-12-17 Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer Hill, Addie Cristea, Mihaela He, Miaoling Frankel, Paul Neuhausen, Susan Pal, Sumanta K Jones, Jeremy O J Cancer Res Ther Oncol Article We sought to evaluate androgen receptor (AR) and PI3K pathway activity in ovarian cancer cell lines and tissue and determine if either pathway was correlated with growth of ovarian cancers. AR expression and activity were quantified using immunohistochemistry (IHC) and RT-qPCR in six ovarian cancer cell lines and 51 tissue samples. Phospho-mTOR and AKT expression were quantified by IHC as well. Cell growth was assessed in the presence of AR modulating drugs and metformin. We found that despite robust AR expression and activity, no cell line was dependent on androgen for growth. However, metformin inhibited activity in five of the six cell lines. Patient tissues had large variation in AR expression and activity, as well as in expression of phospho-mTOR and AKT, but none of these variables correlated with progression-free survival (PFS). AR expression and activity did not predict the dependence of ovarian cancer cell lines on androgens for growth, and AR expression and activity did not correlate with PFS. This result suggests that AR expression as a criterion for patient selection for clinical trials evaluating molecules targeting AR may not predict response for ovarian cancer patients. 2019-05-07 2019-03 /pmc/articles/PMC8682960/ /pubmed/34926721 http://dx.doi.org/10.17303/jcrto.2019.7.103 Text en https://creativecommons.org/licenses/by/3.0/Published by the JScholar under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Article
Hill, Addie
Cristea, Mihaela
He, Miaoling
Frankel, Paul
Neuhausen, Susan
Pal, Sumanta K
Jones, Jeremy O
Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer
title Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer
title_full Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer
title_fullStr Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer
title_full_unstemmed Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer
title_short Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer
title_sort androgen receptor and pi3k pathway activity in ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8682960/
https://www.ncbi.nlm.nih.gov/pubmed/34926721
http://dx.doi.org/10.17303/jcrto.2019.7.103
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