Expression of the p53 target Wig-1 is associated with HPV status and patient survival in cervical carcinoma

The p53 target gene WIG-1 (ZMAT3) is located in chromosomal region 3q26, that is frequently amplified in human tumors, including cervical cancer. We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervic...

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Published in:PloS one 2014-11, Vol.9 (11), p.e111125-e111125
Main Authors: Xu, Li-Di, Muller, Susanne, Thoppe, Srinivasan R, Hellborg, Fredrik, Kanter, Lena, Lerner, Mikael, Zheng, Biying, Lagercrantz, Svetlana Bajalica, Grandér, Dan, Wallin, Keng Ling, Wiman, Klas G, Larsson, Catharina, Andersson, Sonia
Format: Article
Language:English
Subjects:
Apoptosis
Biology and Life Sciences
Biotechnology
Cancer
Carcinoma
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell cycle
Cell death
Cell Line, Tumor
Cell Nucleus - metabolism
Cervical cancer
Cervical carcinoma
Cervix
Children & youth
Childrens health
Chromosome 3
Chromosomes
Chromosomes, Human, Pair 3 - genetics
Comparative analysis
Cytogenetics
Female
Gene expression
Gene Expression Regulation, Neoplastic
Genetic Loci - genetics
Gynecology
Hospitals
Human papillomavirus
Humans
Hybridization
Immunohistochemistry
Kinases
Lesions
Medical prognosis
Medicin och hälsovetenskap
Medicine and Health Sciences
Neoplasm Grading
Neoplasm Staging
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Obstetrics
Oncology
p53 Protein
Papillomaviridae - physiology
Papillomavirus infections
Pathology
Patient outcomes
Prognosis
Proteins
RNA
RNA-Binding Proteins
Senescence
Southern blotting
Staining
Survival
Survival Analysis
Telomerase
Tumor cell lines
Tumor proteins
Tumor Suppressor Protein p53 - metabolism
Tumors
Uterine Cervical Neoplasms - diagnosis
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - pathology
Uterine Cervical Neoplasms - virology
Womens health
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cited_by cdi_FETCH-LOGICAL-c780t-6e755eef0d8f812b6d336d5060064d85c61d15284acaeddc97cb8906ab2905b53
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container_end_page e111125
container_issue 11
container_start_page e111125
container_title PloS one
container_volume 9
creator Xu, Li-Di
Muller, Susanne
Thoppe, Srinivasan R
Hellborg, Fredrik
Kanter, Lena
Lerner, Mikael
Zheng, Biying
Lagercrantz, Svetlana Bajalica
Grandér, Dan
Wallin, Keng Ling
Wiman, Klas G
Larsson, Catharina
Andersson, Sonia
description The p53 target gene WIG-1 (ZMAT3) is located in chromosomal region 3q26, that is frequently amplified in human tumors, including cervical cancer. We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3) by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3) than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p = 0.002) and in adenocarcinomas as compared to squamous cell lesions (p
doi_str_mv 10.1371/journal.pone.0111125
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We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3) by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3) than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p = 0.002) and in adenocarcinomas as compared to squamous cell lesions (p&lt;0.0001). Cases with moderate nuclear Wig-1 staining and positive cytoplasmic Wig-1 staining showed longer survival than patients with strong nuclear and negative cytoplasmic staining (p = 0.042). Nuclear Wig-1 expression levels were positively associated with age at diagnosis (p = 0.023) and histologic grade (p = 0.034). 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We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3) by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3) than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p = 0.002) and in adenocarcinomas as compared to squamous cell lesions (p&lt;0.0001). Cases with moderate nuclear Wig-1 staining and positive cytoplasmic Wig-1 staining showed longer survival than patients with strong nuclear and negative cytoplasmic staining (p = 0.042). Nuclear Wig-1 expression levels were positively associated with age at diagnosis (p = 0.023) and histologic grade (p = 0.034). 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genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell cycle</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cell Nucleus - metabolism</topic><topic>Cervical cancer</topic><topic>Cervical carcinoma</topic><topic>Cervix</topic><topic>Children &amp; youth</topic><topic>Childrens health</topic><topic>Chromosome 3</topic><topic>Chromosomes</topic><topic>Chromosomes, Human, Pair 3 - genetics</topic><topic>Comparative analysis</topic><topic>Cytogenetics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic Loci - genetics</topic><topic>Gynecology</topic><topic>Hospitals</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Immunohistochemistry</topic><topic>Kinases</topic><topic>Lesions</topic><topic>Medical prognosis</topic><topic>Medicin och hälsovetenskap</topic><topic>Medicine and Health Sciences</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Staging</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Obstetrics</topic><topic>Oncology</topic><topic>p53 Protein</topic><topic>Papillomaviridae - physiology</topic><topic>Papillomavirus infections</topic><topic>Pathology</topic><topic>Patient outcomes</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>RNA</topic><topic>RNA-Binding Proteins</topic><topic>Senescence</topic><topic>Southern blotting</topic><topic>Staining</topic><topic>Survival</topic><topic>Survival Analysis</topic><topic>Telomerase</topic><topic>Tumor cell lines</topic><topic>Tumor proteins</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumors</topic><topic>Uterine Cervical Neoplasms - diagnosis</topic><topic>Uterine Cervical Neoplasms - genetics</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Uterine Cervical Neoplasms - virology</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Li-Di</creatorcontrib><creatorcontrib>Muller, Susanne</creatorcontrib><creatorcontrib>Thoppe, Srinivasan R</creatorcontrib><creatorcontrib>Hellborg, Fredrik</creatorcontrib><creatorcontrib>Kanter, Lena</creatorcontrib><creatorcontrib>Lerner, Mikael</creatorcontrib><creatorcontrib>Zheng, Biying</creatorcontrib><creatorcontrib>Lagercrantz, Svetlana Bajalica</creatorcontrib><creatorcontrib>Grandér, Dan</creatorcontrib><creatorcontrib>Wallin, Keng Ling</creatorcontrib><creatorcontrib>Wiman, Klas G</creatorcontrib><creatorcontrib>Larsson, Catharina</creatorcontrib><creatorcontrib>Andersson, Sonia</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Science in Context</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing &amp; Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Li-Di</au><au>Muller, Susanne</au><au>Thoppe, Srinivasan R</au><au>Hellborg, Fredrik</au><au>Kanter, Lena</au><au>Lerner, Mikael</au><au>Zheng, Biying</au><au>Lagercrantz, Svetlana Bajalica</au><au>Grandér, Dan</au><au>Wallin, Keng Ling</au><au>Wiman, Klas G</au><au>Larsson, Catharina</au><au>Andersson, Sonia</au><au>Maki, Carl G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of the p53 target Wig-1 is associated with HPV status and patient survival in cervical carcinoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-07</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e111125</spage><epage>e111125</epage><pages>e111125-e111125</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The p53 target gene WIG-1 (ZMAT3) is located in chromosomal region 3q26, that is frequently amplified in human tumors, including cervical cancer. We have examined the status of WIG-1 and the encoded Wig-1 protein in cervical carcinoma cell lines and tumor tissue samples. Our analysis of eight cervical cancer lines (Ca Ski, ME-180, MS751, SiHa, SW756, C-4I, C-33A, and HT-3) by spectral karyotype, comparative genomic hybridization and Southern blotting revealed WIG-1 is not the primary target for chromosome 3 gains. However, WIG-1/Wig-1 were readily expressed and WIG-1 mRNA expression was higher in the two HPV-negative cervical cell lines (C33-A, HT-3) than in HPV-positive lines. We then assessed Wig-1 expression by immunohistochemistry in 38 cervical tumor samples. We found higher nuclear Wig-1 expression levels in HPV-negative compared to HPV positive cases (p = 0.002) and in adenocarcinomas as compared to squamous cell lesions (p&lt;0.0001). Cases with moderate nuclear Wig-1 staining and positive cytoplasmic Wig-1 staining showed longer survival than patients with strong nuclear and negative cytoplasmic staining (p = 0.042). Nuclear Wig-1 expression levels were positively associated with age at diagnosis (p = 0.023) and histologic grade (p = 0.034). These results are consistent with a growth-promoting and/or anti-cell death function of nuclear Wig-1 and suggest that Wig-1 expression can serve as a prognostic marker in cervical carcinoma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25379706</pmid><doi>10.1371/journal.pone.0111125</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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1932-6203
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source Open Access: PubMed Central; Publicly Available Content Database
subjects Apoptosis
Biology and Life Sciences
Biotechnology
Cancer
Carcinoma
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell cycle
Cell death
Cell Line, Tumor
Cell Nucleus - metabolism
Cervical cancer
Cervical carcinoma
Cervix
Children & youth
Childrens health
Chromosome 3
Chromosomes
Chromosomes, Human, Pair 3 - genetics
Comparative analysis
Cytogenetics
Female
Gene expression
Gene Expression Regulation, Neoplastic
Genetic Loci - genetics
Gynecology
Hospitals
Human papillomavirus
Humans
Hybridization
Immunohistochemistry
Kinases
Lesions
Medical prognosis
Medicin och hälsovetenskap
Medicine and Health Sciences
Neoplasm Grading
Neoplasm Staging
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Obstetrics
Oncology
p53 Protein
Papillomaviridae - physiology
Papillomavirus infections
Pathology
Patient outcomes
Prognosis
Proteins
RNA
RNA-Binding Proteins
Senescence
Southern blotting
Staining
Survival
Survival Analysis
Telomerase
Tumor cell lines
Tumor proteins
Tumor Suppressor Protein p53 - metabolism
Tumors
Uterine Cervical Neoplasms - diagnosis
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - pathology
Uterine Cervical Neoplasms - virology
Womens health
title Expression of the p53 target Wig-1 is associated with HPV status and patient survival in cervical carcinoma
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