Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes

Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorl...

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Published inCancer biology & therapy Vol. 19; no. 9; pp. 773 - 785
Main Authors Rajagopalan, Pavithra, Patel, Krishna, Jain, Ankit P., Nanjappa, Vishalakshi, Datta, Keshava K., Subbannayya, Tejaswini, Mangalaparthi, Kiran K., Kumari, Anjali, Manoharan, Malini, Coral, Karunakaran, Murugan, Sakthivel, Nair, Bipin, Prasad, T. S. Keshava, Mathur, Premendu P., Gupta, Ravi, Gupta, Rohit, Khanna-Gupta, Arati, Califano, Joseph, Sidransky, David, Gowda, Harsha, Chatterjee, Aditi
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 02.09.2018
Subjects
Biomarkers
carcinogenesis
Cell Transformation, Neoplastic
chronic exposure
Environmental Exposure
Gene Expression Profiling
high-throughput
Humans
Keratinocytes - metabolism
Mouth Mucosa - cytology
Orbitrap Fusion
Phenotype
Proteome
Proteomics - methods
Research Paper
smoking
Smoking - adverse effects
Tobacco Use - adverse effects
Transcriptome
Whole Exome Sequencing
Orbitrap Fusion
chronic exposure
carcinogenesis
high-throughput
smoking
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Abstract Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood. We therefore sought to investigate the adverse effects of cigarette smoke/chewing tobacco exposure in oral keratinocytes (OKF6/TERT1). OKF6/TERT1 cells acquired oncogenic phenotype after treating with cigarette smoke/chewing tobacco for a period of 8 months. We employed whole exome sequencing (WES) and quantitative proteomics to investigate the molecular alterations in oral keratinocytes chronically exposed to smoke/ chewing tobacco. Exome sequencing revealed distinct mutational spectrum and copy number alterations in smoke/ chewing tobacco treated cells. We also observed differences in proteomic alterations. Proteins downstream of MAPK1 and EGFR were dysregulated in smoke and chewing tobacco exposed cells, respectively. This study can serve as a reference for fundamental damages on oral cells as a consequence of exposure to different forms of tobacco.
AbstractList Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood. We therefore sought to investigate the adverse effects of cigarette smoke/chewing tobacco exposure in oral keratinocytes (OKF6/TERT1). OKF6/TERT1 cells acquired oncogenic phenotype after treating with cigarette smoke/chewing tobacco for a period of 8 months. We employed whole exome sequencing (WES) and quantitative proteomics to investigate the molecular alterations in oral keratinocytes chronically exposed to smoke/ chewing tobacco. Exome sequencing revealed distinct mutational spectrum and copy number alterations in smoke/ chewing tobacco treated cells. We also observed differences in proteomic alterations. Proteins downstream of MAPK1 and EGFR were dysregulated in smoke and chewing tobacco exposed cells, respectively. This study can serve as a reference for fundamental damages on oral cells as a consequence of exposure to different forms of tobacco.
Author Nanjappa, Vishalakshi
Subbannayya, Tejaswini
Prasad, T. S. Keshava
Nair, Bipin
Murugan, Sakthivel
Datta, Keshava K.
Patel, Krishna
Manoharan, Malini
Califano, Joseph
Mangalaparthi, Kiran K.
Sidransky, David
Coral, Karunakaran
Chatterjee, Aditi
Mathur, Premendu P.
Rajagopalan, Pavithra
Gupta, Rohit
Gupta, Ravi
Jain, Ankit P.
Kumari, Anjali
Khanna-Gupta, Arati
Gowda, Harsha
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Snippet Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary...
SourceID pubmedcentral
crossref
pubmed
informaworld
SourceType Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage 773
SubjectTerms Biomarkers
carcinogenesis
Cell Transformation, Neoplastic
chronic exposure
Environmental Exposure
Gene Expression Profiling
high-throughput
Humans
Keratinocytes - metabolism
Mouth Mucosa - cytology
Orbitrap Fusion
Phenotype
Proteome
Proteomics - methods
Research Paper
smoking
Smoking - adverse effects
Tobacco Use - adverse effects
Transcriptome
Whole Exome Sequencing
Title Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes
URI https://www.tandfonline.com/doi/abs/10.1080/15384047.2018.1470724
https://www.ncbi.nlm.nih.gov/pubmed/29723088
https://pubmed.ncbi.nlm.nih.gov/PMC6154853
Volume 19
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