Frequent presence of incomplete HPV16 E7 ORFs in lung carcinomas: Memories of viral infection

Krikelis, Dimitrios; Tzimagiorgis, Georgios; Georgiou, Elisavet; Destouni, Chariklia; Αγοραστός, Θεόδωρος; Haitoglou, Costas; Kouidou, Sofia

doi:10.1016/j.jcv.2010.07.020

Cited by 12 publications

(8 citation statements)

References 57 publications

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“…Afterwards, a growing body of epidemiological evidence from different countries has shown that the positive rate of high-risk HPV-16/18 DNA and E6 and E7 oncogenes in NSCLC was much higher than that in benign lung neoplasms [9]–[16], wherein HPV-16 was the most prevalent HPV genotype with frequent E6 / E7 oncogene expression [10], [13], [16]. It is worth noting that the prevalence of HPV infection in clinical specimens of bronchial carcinomas is widely divergent in different geographic regions and histological tissue types, ranged from 0.0 to 100% [17], [18].…”

Section: Introductionmentioning

confidence: 99%

Roles of PI3K/Akt and c-Jun Signaling Pathways in Human Papillomavirus Type 16 Oncoprotein-Induced HIF-1α, VEGF, and IL-8 Expression and In Vitro Angiogenesis in Non-Small Cell Lung Cancer Cells

et al. 2014

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Background and ObjectivesHuman papillomavirus (HPV)-16 infection may be related to non-smoking associated lung cancer. Our previous studies have found that HPV-16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells. In this study, we further investigated the roles of PI3K/Akt and c-Jun signaling pathways in it.MethodsHuman NSCLC cell lines, A549 and NCI-H460, were stably transfected with pEGFP-16 E6 or E7 plasmids. Western blotting was performed to analyze the expression of HIF-1α, p-Akt, p-P70S6K, p-P85S6K, p-mTOR, p-JNK, and p-c-Jun proteins. VEGF and IL-8 protein secretion and mRNA levels were determined by ELISA and Real-time PCR, respectively. The in vitro angiogenesis was observed by human umbilical vein endothelial cells (HUVECs) tube formation assay. Co-immunoprecipitation was performed to analyze the interaction between c-Jun and HIF-1α.ResultsHPV-16 E6 and E7 oncoproteins promoted the activation of Akt, P70S6K, P85S6K, mTOR, JNK, and c-Jun. LY294002, a PI3K inhibitor, inhibited HPV-16 oncoprotein-induced activation of Akt, P70S6K, and P85S6K, expression of HIF-1α, VEGF, and IL-8, and in vitro angiogenesis. c-Jun knockdown by specific siRNA abolished HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Additionally, HPV-16 oncoproteins promoted HIF-1α protein stability via blocking proteasome degradation pathway, but c-Jun knockdown abrogated this effect. Furthermore, HPV-16 oncoproteins increased the quantity of c-Jun binding to HIF-1α.ConclusionsPI3K/Akt signaling pathway and c-Jun are involved in HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Moreover, HPV-16 oncoproteins promoted HIF-1α protein stability possibly through enhancing the interaction between c-Jun and HIF-1α, thus making a contribution to angiogenesis in NSCLC cells.

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Section: Introductionmentioning

confidence: 99%

Roles of PI3K/Akt and c-Jun Signaling Pathways in Human Papillomavirus Type 16 Oncoprotein-Induced HIF-1α, VEGF, and IL-8 Expression and In Vitro Angiogenesis in Non-Small Cell Lung Cancer Cells

et al. 2014

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“…In contrast, via a manual search we were able to identify four studies that met the selection criteria of the systematic review by Zhai et al [ 26 ], but were not included [ 36 - 39 ]. Of them, two studies [ 38 , 39 ] were published after their search was closed in March 2014, whereas two studies [ 36 , 37 ] were published before, which shows the importance of a hand search. Yu et al [ 39 ] overlaps with two other studies presented by the same authors based on the same data sources [ 31 , 35 ], and thus, studies for a future meta-analysis should be selected carefully.…”

Section: Discussionmentioning

confidence: 99%

Human papillomavirus infection and risk of lung cancer in never-smokers and women: an ‘adaptive’ meta-analysis

Bae¹,

Kim²

2015

Epidemiol Health

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OBJECTIVES:The incidence of lung cancer in Koreans is increasing in women and in both men and women with a never-smoking history. Human papillomavirus (HPV) infection has been suggested as a modifiable risk factor of lung cancer in never-smokers and women (LCNSW). This systematic review (SR) aimed to evaluate an association between HPV infection and lung cancer risk in LCNSW.METHODS:Based on a prior SR and some expert reviews, we identified refereed, cited, or related articles using the PubMed and Scopus databases. All case-control studies that reported the odds ratio of HPV infection in LCNSW were selected. An estimate of the summary odds ratio (SOR) with 95% confidence intervals (CI) was calculated.RESULTS:A total of four case-control studies were included. The fixed-effect model was applied because of homogeneity (I-squared=0.0%). The SORs in women and in never-smokers were 5.32 (95% CI, 1.75 to 16.17) and 4.78 (2.25 to 10.15) respectively.CONCLUSIONS:These results showed a significant effect of HPV infection in LCNSW. It is evident that developing a preventive plan against LCNSW may be necessary.

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“…So far, HPV16 has been the most frequent high-risk HPV genotype found in lung carcinomas around the world [5] with frequent E6/E7 oncogene expression [11]. High-risk HPV integration into the host genome [12] was previously reported to occur in lung cancer [13].…”

Section: Introductionmentioning

confidence: 99%

Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells

et al. 2012

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The smoking habit is the most important, but not a sufficient cause for lung cancer development. Several studies have reported the human papillomavirus type 16 (HPV16) presence and E6 and E7 transcripts expression in lung carcinoma cases from different geographical regions. The possible interaction between HPV infection and smoke carcinogens, however, remains unclear. In this study we address a potential cooperation between tobacco smoke and HPV16 E6 and E7 oncoproteins for alterations in proliferative and tumorigenic properties of lung epithelial cells. A549 (alveolar, tumoral) and BEAS-2B (bronchial, non-tumoral) cell lines were stably transfected with recombinant pLXSN vectors expressing HPV16 E6 and E7 oncoproteins and exposed to cigarette smoke condensate (CSC) at different concentrations. HPV16 E6 and E7 expression was associated with loss of p53 stability, telomerase (hTERT) and p16INK4A overexpression in BEAS-2B cells as demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). In A549 cells we observed downregulation of p53 but not a significant increase of hTERT transcripts. In addition, the HPV16 E6/E7 transfected cell lines showed an increased proliferation rate and anchorage-independent growth in a HPV16 E6 and E7 expression-dependent manner. Moreover, both HPV16 E6/E7 and mock transfected cells showed an increased proliferation rate and anchorage-independent growth in the presence of 0.1 and 10 µg/mL CSC. However, this increase was significantly greater in HPV16 E6/E7 transfected cells (p<0.001). Data were confirmed by FCSE proliferation assay. The results obtained in this study are suggestive of a functional interaction between tobacco smoke and HPV16 E6/E7 oncoproteins for malignant transformation and tumorigenesis of lung epithelial cells. More studies are warranted in order to dissect the molecular mechanisms involved in this cooperation.

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Frequent presence of incomplete HPV16 E7 ORFs in lung carcinomas: Memories of viral infection

Cited by 12 publications

References 57 publications

Roles of PI3K/Akt and c-Jun Signaling Pathways in Human Papillomavirus Type 16 Oncoprotein-Induced HIF-1α, VEGF, and IL-8 Expression and In Vitro Angiogenesis in Non-Small Cell Lung Cancer Cells

Roles of PI3K/Akt and c-Jun Signaling Pathways in Human Papillomavirus Type 16 Oncoprotein-Induced HIF-1α, VEGF, and IL-8 Expression and In Vitro Angiogenesis in Non-Small Cell Lung Cancer Cells

Human papillomavirus infection and risk of lung cancer in never-smokers and women: an ‘adaptive’ meta-analysis

Functional Interaction between Human Papillomavirus Type 16 E6 and E7 Oncoproteins and Cigarette Smoke Components in Lung Epithelial Cells

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