Cargando…
MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity
Localized prostate cancer develops very slowly in most men, with the androgen receptor (AR) and MYC transcription factors amongst the most well-characterized drivers of prostate tumorigenesis. Canonically, MYC up-regulation in luminal prostate cancer cells functions to oppose the terminally differen...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441006/ https://www.ncbi.nlm.nih.gov/pubmed/32681068 http://dx.doi.org/10.1038/s41388-020-01389-7 |
_version_ | 1783573225787097088 |
---|---|
author | Whitlock, Nichelle C. Trostel, Shana Y. Wilkinson, Scott Terrigino, Nicholas T. Hennigan, S. Thomas Lake, Ross Carrabba, Nicole V. Atway, Rayann Walton, Elizabeth D. Gryder, Berkley E. Capaldo, Brian J. Ye, Huihui Sowalsky, Adam G. |
author_facet | Whitlock, Nichelle C. Trostel, Shana Y. Wilkinson, Scott Terrigino, Nicholas T. Hennigan, S. Thomas Lake, Ross Carrabba, Nicole V. Atway, Rayann Walton, Elizabeth D. Gryder, Berkley E. Capaldo, Brian J. Ye, Huihui Sowalsky, Adam G. |
author_sort | Whitlock, Nichelle C. |
collection | PubMed |
description | Localized prostate cancer develops very slowly in most men, with the androgen receptor (AR) and MYC transcription factors amongst the most well-characterized drivers of prostate tumorigenesis. Canonically, MYC up-regulation in luminal prostate cancer cells functions to oppose the terminally differentiating effects of AR. However, the effects of MYC up-regulation are pleiotropic and inconsistent with a poorly proliferative phenotype. Here we show that increased MYC expression and activity are associated with the down-regulation of MEIS1, a HOX-family transcription factor. Using RNA-seq to profile a series of human prostate cancer specimens laser capture microdissected on the basis of MYC immunohistochemistry, MYC activity, and MEIS1 expression were inversely correlated. Knockdown of MYC expression in prostate cancer cells increased the expression of MEIS1 and increased the occupancy of MYC at the MEIS1 locus. Finally, we show in laser capture microdissected human prostate cancer samples and the prostate TCGA cohort that MEIS1 expression is inversely proportional to AR activity as well as HOXB13, a known interacting protein of both AR and MEIS1. Collectively, our data demonstrate that elevated MYC in a subset of primary prostate cancers functions in a negative role in regulating MEIS1 expression, and that this down-regulation may contribute to MYC-driven development and progression. |
format | Online Article Text |
id | pubmed-7441006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-74410062020-08-28 MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity Whitlock, Nichelle C. Trostel, Shana Y. Wilkinson, Scott Terrigino, Nicholas T. Hennigan, S. Thomas Lake, Ross Carrabba, Nicole V. Atway, Rayann Walton, Elizabeth D. Gryder, Berkley E. Capaldo, Brian J. Ye, Huihui Sowalsky, Adam G. Oncogene Article Localized prostate cancer develops very slowly in most men, with the androgen receptor (AR) and MYC transcription factors amongst the most well-characterized drivers of prostate tumorigenesis. Canonically, MYC up-regulation in luminal prostate cancer cells functions to oppose the terminally differentiating effects of AR. However, the effects of MYC up-regulation are pleiotropic and inconsistent with a poorly proliferative phenotype. Here we show that increased MYC expression and activity are associated with the down-regulation of MEIS1, a HOX-family transcription factor. Using RNA-seq to profile a series of human prostate cancer specimens laser capture microdissected on the basis of MYC immunohistochemistry, MYC activity, and MEIS1 expression were inversely correlated. Knockdown of MYC expression in prostate cancer cells increased the expression of MEIS1 and increased the occupancy of MYC at the MEIS1 locus. Finally, we show in laser capture microdissected human prostate cancer samples and the prostate TCGA cohort that MEIS1 expression is inversely proportional to AR activity as well as HOXB13, a known interacting protein of both AR and MEIS1. Collectively, our data demonstrate that elevated MYC in a subset of primary prostate cancers functions in a negative role in regulating MEIS1 expression, and that this down-regulation may contribute to MYC-driven development and progression. Nature Publishing Group UK 2020-07-17 2020 /pmc/articles/PMC7441006/ /pubmed/32681068 http://dx.doi.org/10.1038/s41388-020-01389-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Whitlock, Nichelle C. Trostel, Shana Y. Wilkinson, Scott Terrigino, Nicholas T. Hennigan, S. Thomas Lake, Ross Carrabba, Nicole V. Atway, Rayann Walton, Elizabeth D. Gryder, Berkley E. Capaldo, Brian J. Ye, Huihui Sowalsky, Adam G. MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity |
title | MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity |
title_full | MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity |
title_fullStr | MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity |
title_full_unstemmed | MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity |
title_short | MEIS1 down-regulation by MYC mediates prostate cancer development through elevated HOXB13 expression and AR activity |
title_sort | meis1 down-regulation by myc mediates prostate cancer development through elevated hoxb13 expression and ar activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441006/ https://www.ncbi.nlm.nih.gov/pubmed/32681068 http://dx.doi.org/10.1038/s41388-020-01389-7 |
work_keys_str_mv | AT whitlocknichellec meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT trostelshanay meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT wilkinsonscott meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT terriginonicholast meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT hennigansthomas meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT lakeross meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT carrabbanicolev meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT atwayrayann meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT waltonelizabethd meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT gryderberkleye meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT capaldobrianj meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT yehuihui meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity AT sowalskyadamg meis1downregulationbymycmediatesprostatecancerdevelopmentthroughelevatedhoxb13expressionandaractivity |