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Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells
Preoperative progesterone intervention has been shown to confer a survival benefit to breast cancer patients independently of their progesterone receptor (PR) status. This observation raises the question how progesterone affects the outcome of PR-negative cancer. Here, using microarray and RNA-Seq–b...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298595/ https://www.ncbi.nlm.nih.gov/pubmed/30337371 http://dx.doi.org/10.1074/jbc.RA118.002894 |
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author | Godbole, Mukul Togar, Trupti Patel, Kuldeep Dharavath, Bhasker Yadav, Neelima Janjuha, Sharan Gardi, Nilesh Tiwary, Kanishka Terwadkar, Prachi Desai, Sanket Prasad, Ratnam Dhamne, Hemant Karve, Kunal Salunkhe, Sameer Kawle, Dhananjay Chandrani, Pratik Dutt, Shilpee Gupta, Sudeep Badwe, Rajendra A. Dutt, Amit |
author_facet | Godbole, Mukul Togar, Trupti Patel, Kuldeep Dharavath, Bhasker Yadav, Neelima Janjuha, Sharan Gardi, Nilesh Tiwary, Kanishka Terwadkar, Prachi Desai, Sanket Prasad, Ratnam Dhamne, Hemant Karve, Kunal Salunkhe, Sameer Kawle, Dhananjay Chandrani, Pratik Dutt, Shilpee Gupta, Sudeep Badwe, Rajendra A. Dutt, Amit |
author_sort | Godbole, Mukul |
collection | PubMed |
description | Preoperative progesterone intervention has been shown to confer a survival benefit to breast cancer patients independently of their progesterone receptor (PR) status. This observation raises the question how progesterone affects the outcome of PR-negative cancer. Here, using microarray and RNA-Seq–based gene expression profiling and ChIP-Seq analyses of breast cancer cells, we observed that the serum- and glucocorticoid-regulated kinase gene (SGK1) and the tumor metastasis–suppressor gene N-Myc downstream regulated gene 1 (NDRG1) are up-regulated and that the microRNAs miR-29a and miR-101-1 targeting the 3′-UTR of SGK1 are down-regulated in response to progesterone. We further demonstrate a dual-phase transcriptional and post-transcriptional regulation of SGK1 in response to progesterone, leading to an up-regulation of NDRG1 that is mediated by a set of genes regulated by the transcription factor AP-1. We found that NDRG1, in turn, inactivates a set of kinases, impeding the invasion and migration of breast cancer cells. In summary, we propose a model for the mode of action of progesterone in breast cancer. This model helps decipher the molecular basis of observations in a randomized clinical trial of the effect of progesterone on breast cancer and has therefore the potential to improve the prognosis of breast cancer patients receiving preoperative progesterone treatment. |
format | Online Article Text |
id | pubmed-6298595 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62985952018-12-18 Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells Godbole, Mukul Togar, Trupti Patel, Kuldeep Dharavath, Bhasker Yadav, Neelima Janjuha, Sharan Gardi, Nilesh Tiwary, Kanishka Terwadkar, Prachi Desai, Sanket Prasad, Ratnam Dhamne, Hemant Karve, Kunal Salunkhe, Sameer Kawle, Dhananjay Chandrani, Pratik Dutt, Shilpee Gupta, Sudeep Badwe, Rajendra A. Dutt, Amit J Biol Chem Molecular Bases of Disease Preoperative progesterone intervention has been shown to confer a survival benefit to breast cancer patients independently of their progesterone receptor (PR) status. This observation raises the question how progesterone affects the outcome of PR-negative cancer. Here, using microarray and RNA-Seq–based gene expression profiling and ChIP-Seq analyses of breast cancer cells, we observed that the serum- and glucocorticoid-regulated kinase gene (SGK1) and the tumor metastasis–suppressor gene N-Myc downstream regulated gene 1 (NDRG1) are up-regulated and that the microRNAs miR-29a and miR-101-1 targeting the 3′-UTR of SGK1 are down-regulated in response to progesterone. We further demonstrate a dual-phase transcriptional and post-transcriptional regulation of SGK1 in response to progesterone, leading to an up-regulation of NDRG1 that is mediated by a set of genes regulated by the transcription factor AP-1. We found that NDRG1, in turn, inactivates a set of kinases, impeding the invasion and migration of breast cancer cells. In summary, we propose a model for the mode of action of progesterone in breast cancer. This model helps decipher the molecular basis of observations in a randomized clinical trial of the effect of progesterone on breast cancer and has therefore the potential to improve the prognosis of breast cancer patients receiving preoperative progesterone treatment. American Society for Biochemistry and Molecular Biology 2018-12-14 2018-10-18 /pmc/articles/PMC6298595/ /pubmed/30337371 http://dx.doi.org/10.1074/jbc.RA118.002894 Text en © 2018 Godbole et al. Author's Choice—Final version open access under the terms of the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0) . |
spellingShingle | Molecular Bases of Disease Godbole, Mukul Togar, Trupti Patel, Kuldeep Dharavath, Bhasker Yadav, Neelima Janjuha, Sharan Gardi, Nilesh Tiwary, Kanishka Terwadkar, Prachi Desai, Sanket Prasad, Ratnam Dhamne, Hemant Karve, Kunal Salunkhe, Sameer Kawle, Dhananjay Chandrani, Pratik Dutt, Shilpee Gupta, Sudeep Badwe, Rajendra A. Dutt, Amit Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells |
title | Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells |
title_full | Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells |
title_fullStr | Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells |
title_full_unstemmed | Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells |
title_short | Up-regulation of the kinase gene SGK1 by progesterone activates the AP-1–NDRG1 axis in both PR-positive and -negative breast cancer cells |
title_sort | up-regulation of the kinase gene sgk1 by progesterone activates the ap-1–ndrg1 axis in both pr-positive and -negative breast cancer cells |
topic | Molecular Bases of Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298595/ https://www.ncbi.nlm.nih.gov/pubmed/30337371 http://dx.doi.org/10.1074/jbc.RA118.002894 |
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