Expression of p53 and its homolog, p73, in HPV DNA positive oesophageal squamous cell carcinomas

Matsha, Tandi E.; Donninger, Howard; Erasmus, Rajief T.; Hendricks, Denver T.; Stepien, A.; Parker, M. Iqbal

doi:10.1016/j.virol.2007.07.025

Cited by 24 publications

(24 citation statements)

References 46 publications

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“…Some of the low risk areas include North America, along with countries in Western Asia and Northern and Southern Europe, where the incidence rates range from 1.5 to 6.0 of 100,000. High-risk areas include South Africa, China, Iran, and countries in Eastern Africa, where the incidence rates range from 10 to 25 of 100,000 (35,36). In addition to the known risk factors such as alcohol and tobacco, gastroesophageal reflux disease, nutritional deficiencies, numerous studies have detected HPV) DNA in esophageal cancer specimens, implicating HPV infection as a further risk factor in the development of esophageal cancer (37,38).…”

Section: Discussionmentioning

confidence: 99%

Critical Role for the Receptor Tyrosine Kinase EPHB4 in Esophageal Cancers

et al. 2013

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Esophageal cancer incidence is increasing and has few treatment options. In studying receptor tyrosine kinases associated with esophageal cancers, we have identified EPHB4 to be robustly overexpressed in cell lines and primary tumor tissues. In total, 94 squamous cell carcinoma, 82 adenocarcinoma, 25 dysplasia, 13 Barrett esophagus, and 25 adjacent or unrelated normal esophageal tissues were evaluated by immunohistochemistry. EPHB4 expression was significantly higher in all the different histologic categories than in adjacent normal tissues. In 13 esophageal cancer cell lines, 3 of the 9 SCC cell lines and 2 of the 4 adenocarcinomas expressed very high levels of EPHB4. An increased gene copy number ranging from 4 to 20 copies was identified in a subset of the overexpressing patient samples and cell lines. We have developed a novel 4-nitroquinoline 1-oxide (4-NQO)-induced mouse model of esophageal cancer that recapitulates the EPHB4 expression in humans. A specific small-molecule inhibitor of EPHB4 decreased cell viability in a timeand dose-dependent manner in 3 of the 4 cell lines tested. The small-molecule inhibitor and an EPHB4 siRNA also decreased cell migration (12%-40% closure in treated vs. 60%-80% in untreated), with decreased phosphorylation of various tyrosyl-containing proteins, EphB4, and its downstream target p125FAK. Finally, in a xenograft tumor model, an EPHB4 inhibitor abrogated tumor growth by approximately 60% compared with untreated control. EphB4 is robustly expressed and potentially serves as a novel biomarker for targeted therapy in esophageal cancers. Cancer Res; 73(1); 184-94. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

Critical Role for the Receptor Tyrosine Kinase EPHB4 in Esophageal Cancers

et al. 2013

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“…Out of the HPV-positive tumours, 50% contained the low-risk HPV-6 DNA and 8% showed HPV-16 DNA. Another study showed that HPV-11 is the predominant type (48%) present in HPV-positive OSCC patients (Matsha et al 2007) in the Transkei region of South Africa. Therefore, the role of low-risk HPV types in tumour development is not very clear.…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis

2009

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Human papillomavirus (HPV) is small, double-stranded DNA virus that infects mucosal and cutaneous epithelial tissue. HPV is sexually transmitted and the viral DNA replicates extrachromosomally. The virus is non-enveloped and has an icosahedral capsid. There are approximately 118 types of HPV, which are characterized as high-risk or low- risk types. High-risk HPVs cause malignant transformation while the low-risk ones cause benign warts and lesions. The expression of E6 and E7 is normally controlled during the normal viral life cycle when viral DNA replicates extrachromosomally. HPV E6 and E7 oncoproteins are overexpressed when the viral genome integrates into the host DNA.Deregulated overexpression of E6 and E7 oncoproteins can cause several changes in cellular pathways and functions leading to malignant transformation of cells and tumorigenesis. In this review, we focus on several cellular mechanisms and pathways that are altered in the presence of E6 and E7, the target proteins of E6 and E7 inside the host cell and how they contribute to the development of the transformed phenotype.

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“…E6AP is a host ubiquitin ligase and it is required by E6 to exert its cellular effects. Since it has been shown that expression of HPV E6 alone can lead to transformation of host cell, we have focussed our studies with E6 only [16,25,39]. However, the role of E6 proteins in oesophageal cancer is not very clear since the lowrisk HPV11 is the predominant type present in the oesophageal cancer specimens in South Africa [47].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analyses of genes differentially expressed by high-risk and low-risk human papilloma virus E6 oncoproteins

Ganguly

2015

VirusDis.

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Human papilloma virus is the causative agent for cervical cancer with 99 % of cervical cancer cases containing HPV. The high risk HPV-16, 18 and 31 are the major causative agents. The low risk HPV-6, 11 have been reported to cause penile, laryngeal, bronchogenic and oesophageal cancer. Since E6 oncoprotein is frequently over expressed in cancers, we did gene expression studies to compare between the E6 genes of high-risk (HPV18) or low-risk (HPV11)stably transfected in epithelial cell line EPC-2 or mock transfected with the basic vector pCDNA3.1. Microarray studies showed a total of 697 genes showing differential expression between the samples. Genes involved in several key cellular processes such as cell adhesion, angiogenesis, transcription regulation, cell cycle regulation and cell division showed altered expression between the samples. Gene Ontology mapping of 44 genes according cellular pathways revealed 13 pathways namely angiogenesis, alzhemier's, Wnt, p53, interleukin, TGF-b, cadherin, integrin, PI3-kinase, catennin, insulin, chemokine and G protein signalling pathways. The microarray results were confirmed by quantitative real-time PCR for some representative genes like IFI27, CTNNA1, OSMR, CYP1B1, TNFSF13, LAMA2 and COL5A3. Analysis of differentially expressed genes by high-risk and lowrisk HPV E6 proteins might help in identification of potential biomarkers for diagnosis, progression and therapy of oesophageal cancer. The understanding of mechanisms of activation of these genes as well as the function of gene products will give a further insight into their roles in oesophageal cancer.

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Expression of p53 and its homolog, p73, in HPV DNA positive oesophageal squamous cell carcinomas

Cited by 24 publications

References 46 publications

Critical Role for the Receptor Tyrosine Kinase EPHB4 in Esophageal Cancers

Critical Role for the Receptor Tyrosine Kinase EPHB4 in Esophageal Cancers

Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis

Transcriptomic analyses of genes differentially expressed by high-risk and low-risk human papilloma virus E6 oncoproteins

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