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Biological Chemistry

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Volume 397, Issue 11


Epigenetic regulation of KLK7 gene expression in pancreatic and cervical cancer cells

Ilangovan Raju
  • Central Arkansas Veterans Healthcare System, 4300 West 7th St., Little Rock, AR 72205, United States of America
  • Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham Street, #753, Little Rock, AR 72205, United States of America
  • Other articles by this author:
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/ Gur P. Kaushal
  • Central Arkansas Veterans Healthcare System, 4300 West 7th St., Little Rock, AR 72205, United States of America
  • Other articles by this author:
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/ Randy S. Haun
  • Corresponding author
  • Central Arkansas Veterans Healthcare System, 4300 West 7th St., Little Rock, AR 72205, United States of America
  • Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham Street, #753, Little Rock, AR 72205, United States of America
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-06-08 | DOI: https://doi.org/10.1515/hsz-2015-0307


Kallikrein-related peptidase 7 (KLK7) is a serine protease encoded within the kallikrein gene cluster located on human chromosome region 19q13.3-13.4. KLK7 is overexpressed in human pancreatic ductal adenocarcinomas (PDACs), but not in normal pancreas. Examination of KLK7 mRNA levels in pancreatic cancer cell lines revealed that it is readily detected in MIA PaCa-2 and PK-1 cells, but not in Panc-1 cells. Treatment of Panc-1 cells with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) significantly induced KLK7 mRNA expression. Similarly, KLK7 is highly expressed in cervical cancer cells, but its expression in the human cervical cancer cell line HeLa is only detected following TSA treatment. Promoter deletion analysis revealed that the proximal -238 promoter region, containing a putative Sp1-binding site, was sufficient for TSA activation of luciferase reporter activity, which was abrogated by the disruption of the Sp1-binding sequence. Consistent with the notion that TSA induced KLK7 expression via Sp1, co-expression of Sp1 with the KLK7-promoter/luciferase construct produced a significant increase in reporter activity. Chromatin immunoprecipitation (ChIP) analysis revealed enriched Sp1 occupancy on the KLK7 promoter following TSA treatment. Similarly, ChIP analysis showed the histone active mark, H3K4Me3, in the KLK7 promoter region was significantly increased after exposure to TSA.

Keywords: chromatin; epigenetics; KLK7; pancreatic cancer; transcription; trichostatin A


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About the article

Received: 2015-12-18

Accepted: 2016-06-05

Published Online: 2016-06-08

Published in Print: 2016-11-01

Citation Information: Biological Chemistry, Volume 397, Issue 11, Pages 1135–1146, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2015-0307.

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