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Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis

The human RNA polymerase II (RNAPII)-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases, including cancer. However, its involvement in breast cancer awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr...

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Detalles Bibliográficos
Autores principales: Zeng, Hao, Xu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617979/
https://www.ncbi.nlm.nih.gov/pubmed/26494790
http://dx.doi.org/10.1101/gad.268722.115
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author Zeng, Hao
Xu, Wei
author_facet Zeng, Hao
Xu, Wei
author_sort Zeng, Hao
collection PubMed
description The human RNA polymerase II (RNAPII)-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases, including cancer. However, its involvement in breast cancer awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr9, the key scaffold subunit in hPAFc, is highly expressed in estrogen receptor α-positive (ERα(+)) luminal breast cancer, and the high expression of Ctr9 correlates with poor prognosis. Knockdown of Ctr9 in ERα(+) breast cancer cells almost completely erased estrogen-regulated transcriptional response. At the molecular level, Ctr9 enhances ERα protein stability, promotes recruitment of ERα and RNAPII, and stimulates transcription elongation and transcription-coupled histone modifications. Knockdown of Ctr9, but not other hPAFc subunits, alters the morphology, proliferative capacity, and tamoxifen sensitivity of ERα(+) breast cancer cells. Together, our study reveals that Ctr9, a key subunit of hPAFc, is a central regulator of estrogen signaling that drives ERα(+) breast tumorigenesis, rendering it a potential target for the treatment of ERα(+) breast cancer.
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spelling pubmed-46179792016-04-15 Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis Zeng, Hao Xu, Wei Genes Dev Research Paper The human RNA polymerase II (RNAPII)-associated factor complex (hPAFc) and its individual subunits have been implicated in human diseases, including cancer. However, its involvement in breast cancer awaits investigation. Using data mining and human breast cancer tissue microarrays, we found that Ctr9, the key scaffold subunit in hPAFc, is highly expressed in estrogen receptor α-positive (ERα(+)) luminal breast cancer, and the high expression of Ctr9 correlates with poor prognosis. Knockdown of Ctr9 in ERα(+) breast cancer cells almost completely erased estrogen-regulated transcriptional response. At the molecular level, Ctr9 enhances ERα protein stability, promotes recruitment of ERα and RNAPII, and stimulates transcription elongation and transcription-coupled histone modifications. Knockdown of Ctr9, but not other hPAFc subunits, alters the morphology, proliferative capacity, and tamoxifen sensitivity of ERα(+) breast cancer cells. Together, our study reveals that Ctr9, a key subunit of hPAFc, is a central regulator of estrogen signaling that drives ERα(+) breast tumorigenesis, rendering it a potential target for the treatment of ERα(+) breast cancer. Cold Spring Harbor Laboratory Press 2015-10-15 /pmc/articles/PMC4617979/ /pubmed/26494790 http://dx.doi.org/10.1101/gad.268722.115 Text en © 2015 Zeng and Xu; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Zeng, Hao
Xu, Wei
Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis
title Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis
title_full Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis
title_fullStr Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis
title_full_unstemmed Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis
title_short Ctr9, a key subunit of PAFc, affects global estrogen signaling and drives ERα-positive breast tumorigenesis
title_sort ctr9, a key subunit of pafc, affects global estrogen signaling and drives erα-positive breast tumorigenesis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617979/
https://www.ncbi.nlm.nih.gov/pubmed/26494790
http://dx.doi.org/10.1101/gad.268722.115
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