Transcriptional regulation of oncogenic protein kinase Cε (PKCε) by STAT1 and Sp1 proteins

Overexpression of PKCε, a kinase associated with tumor aggressiveness and widely implicated in malignant transformation and metastasis, is a hallmark of multiple cancers, including mammary, prostate, and lung cancer. To characterize the mechanisms that control PKCε expression and its up-regulation i...

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Detalles Bibliográficos
Autores principales: Wang, HongBin, Gutierrez Uzquiza, Alvaro, Garg, Rachana, Barrio Real, Laura, Abera, Mahlet B., Lopez Haber, Cynthia, Rosemblit, Cinthia, Lu, Huaisheng, Abba, Martín Carlos, Kazanietz, Marcelo G.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2014
Materias:
Ciencias Médicas
PKCε
cancer cells
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85093
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-85093
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
PKCε
cancer cells
spellingShingle Ciencias Médicas
PKCε
cancer cells
Wang, HongBin
Gutierrez Uzquiza, Alvaro
Garg, Rachana
Barrio Real, Laura
Abera, Mahlet B.
Lopez Haber, Cynthia
Rosemblit, Cinthia
Lu, Huaisheng
Abba, Martín Carlos
Kazanietz, Marcelo G.
Transcriptional regulation of oncogenic protein kinase Cε (PKCε) by STAT1 and Sp1 proteins
topic_facet Ciencias Médicas
PKCε
cancer cells
description Overexpression of PKCε, a kinase associated with tumor aggressiveness and widely implicated in malignant transformation and metastasis, is a hallmark of multiple cancers, including mammary, prostate, and lung cancer. To characterize the mechanisms that control PKCε expression and its up-regulation in cancer, we cloned an ∼1.6-kb promoter segment of the human PKCε gene (<i>PRKCE</i>) that displays elevated transcriptional activity in cancer cells. A comprehensive deletional analysis established two regions rich in Sp1 and STAT1 sites located between -777 and-105 bp (region A) and-921 and-796 bp (region B), respectively, as responsible for the high transcriptional activity observed in cancer cells. A more detailed mutagenesis analysis followed by EMSA and ChIP identified Sp1 sites in positions -668/-659 and-269/-247 as well as STAT1 sites in positions -880/-869 and- 793/-782 as the elements responsible for elevated promoter activity in breast cancer cells relative to normal mammary epithelial cells. RNAi silencing of Sp1 and STAT1 in breast cancer cells reduced PKCε mRNA and protein expression, as well as <i>PRKCE</i> promoter activity. Moreover, a strong correlation was found between PKCε and phospho-Ser-727 (active) STAT1 levels in breast cancer cells. Our results may have significant implications for the development of approaches to target PKCε and its effectors in cancer therapeutics.
format Articulo
Articulo
author Wang, HongBin
Gutierrez Uzquiza, Alvaro
Garg, Rachana
Barrio Real, Laura
Abera, Mahlet B.
Lopez Haber, Cynthia
Rosemblit, Cinthia
Lu, Huaisheng
Abba, Martín Carlos
Kazanietz, Marcelo G.
author_facet Wang, HongBin
Gutierrez Uzquiza, Alvaro
Garg, Rachana
Barrio Real, Laura
Abera, Mahlet B.
Lopez Haber, Cynthia
Rosemblit, Cinthia
Lu, Huaisheng
Abba, Martín Carlos
Kazanietz, Marcelo G.
author_sort Wang, HongBin
title Transcriptional regulation of oncogenic protein kinase Cε (PKCε) by STAT1 and Sp1 proteins
title_short Transcriptional regulation of oncogenic protein kinase Cε (PKCε) by STAT1 and Sp1 proteins
title_full Transcriptional regulation of oncogenic protein kinase Cε (PKCε) by STAT1 and Sp1 proteins
title_fullStr Transcriptional regulation of oncogenic protein kinase Cε (PKCε) by STAT1 and Sp1 proteins
title_full_unstemmed Transcriptional regulation of oncogenic protein kinase Cε (PKCε) by STAT1 and Sp1 proteins
title_sort transcriptional regulation of oncogenic protein kinase cε (pkcε) by stat1 and sp1 proteins
publishDate 2014
url http://sedici.unlp.edu.ar/handle/10915/85093
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