TK1 expression influences pathogenicity by cell cycle progression, cellular migration, and cellular survival in HCC 1806 breast cancer cells

Author:

Bitter Eliza E.ORCID,Skidmore JonathanORCID,Allen Carolyn I.,Erickson Rachel I.ORCID,Morris Rachel M.,Mortimer Toni,Meade Audrey,Brog Rachel,Phares Tim,Townsend Michelle,Pickett Brett E.,O’Neill Kim L.ORCID

Abstract

Breast cancer is the most common cancer diagnosis worldwide accounting for 1 out of every 8 cancer diagnoses. The elevated expression of Thymidine Kinase 1 (TK1) is associated with more aggressive tumor grades, including breast cancer. Recent studies indicate that TK1 may be involved in cancer pathogenesis; however, its direct involvement in breast cancer has not been identified. Here, we evaluate potential pathogenic effects of elevated TK1 expression by comparing HCC 1806 to HCC 1806 TK1-knockdown cancer cells (L133). Transcriptomic profiles of HCC 1806 and L133 cells showed cell cycle progression, apoptosis, and invasion as potential pathogenic pathways affected by TK1 expression. Subsequent in-vitro studies confirmed differences between HCC 1806 and L133 cells in cell cycle phase progression, cell survival, and cell migration. Expression comparison of several factors involved in these pathogenic pathways between HCC 1806 and L133 cells identified p21 and AKT3 transcripts were significantly affected by TK1 expression. Creation of a protein-protein interaction map of TK1 and the pathogenic factors we evaluated predict that the majority of factors evaluated either directly or indirectly interact with TK1. Our findings argue that TK1 elevation directly increases HCC 1806 cell pathogenicity and is likely occurring by p21- and AKT3-mediated mechanisms to promote cell cycle arrest, cellular migration, and cellular survival.

Publisher

Public Library of Science (PLoS)

Subject

Multidisciplinary

Reference100 articles.

1. Nucleic acid metabolism in regenerating rat liver. VI. Soluble enzymes which convert thymidine to thymidine phosphates and DNA;FJ Bollum;Cancer research,1959

2. Regulation and functional contribution of thymidine kinase 1 in repair of DNA damage;YL Chen;The Journal of biological chemistry,2010

3. Human thymidine kinase 1. Regulation in normal and malignant cells;B Munch-Petersen;Advances in enzyme regulation,1995

4. The role of thymidine kinase in cancer diseases;O Topolcan;Expert Opinion on Medical Diagnostics,2008

5. The proliferation marker thymidine kinase 1 in clinical use;J Zhou;Mol Clin Oncol,2013

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3