High level HPV‐16 E7 oncoprotein expression correlates with reduced pRb‐levels in cervical biopsies

Fiedler, Marc; Müller‐Holzner, Elisabeth; Viertler, Hans-Peter; Widschwendter, Andreas; Laich, Andreas; Pfister, Gerald; Spoden, Gilles A.; Jansen‐Dürr, Pidder; Zwerschke, Werner

doi:10.1096/fj.03-1332fje

Cited by 60 publications

(71 citation statements)

References 63 publications

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“…The importance of p53 degradation in HPV-related lung carcinogenesis was suggested by a recent study of lung carcinomas diagnosed in Taiwan, which showed an inverse correlation between HPV-16/18 E6 expression and p53 expression (16). Another important oncoprotein of HPV is E7, whose binding with pRb destabilizes this tumor suppressor protein (17) and induces E2F release and subsequent p16…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas

Baba

Castillo²,

Koriyama³

et al. 2010

Oncol Rep

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Abstract.A number of studies have reported the presence of human papillomavirus (HPV) in lung carcinoma. Interestingly, its detection rate appears to differ histologically and geographically. The present study examined 30 adenocarcinomas and 27 squamous cell carcinomas of the lung in a southern area of Japan, and detected high-risk HPV genome in 9 (30%) adenocarcinomas and 2 (7%) squamous cell carcinomas, using PCR with SPF10 primers and INNO-LiPA HPV genotyping assay. The difference of HPV detection rates in adenocarcinomas and squamous cell carcinomas was statistically significant (P=0.044, Fisher's exact test). HPV-16 was the most prevalent HPV genotype, and was detected in 27% (8/30) of adenocarcinomas and in 7% (2/27) of squamous cell carcinomas. High-risk-HPV positive carcinomas had decreased proportions of pRb (P=0.107) and significantly increased proportions of p16INK4a expressing cells (P=0.031) when compared to HPV-negative lung carcinomas. All HPV-16-positive cases were considered to have an integrated form of HPV-16 but its viral load was low (geometric mean = 0.02 copy per cell). In 20 additional adenocarcinomas treated with gefitinib, a tyrosine kinase inhibitor specific for epidermal growth factor receptor, the presence of HPV was examined. Note that East Asian ethnicity is a predictive factor of gefitinib response. High-risk HPV genome was found in 75% (6/8) of adenocarcinomas with complete or partial response to gefitinib but was not found in the remaining 12, which did not respond to gefitinib. In conclusion, the present study suggests that high-risk HPV may be more strongly related to adenocarcinomas, particularly gefitinib-responsive adenocarcinomas, when compared to squamous cell carcinomas. However, its low viral load makes it difficult to determine the etiological significance of these findings.

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Section: Introductionmentioning

confidence: 99%

Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas

Baba

Castillo²,

Koriyama³

et al. 2010

Oncol Rep

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“…6 A primary role of E6 is its association with p53 preventing growth arrest or apoptosis in response to E7-mediated cell cycle entry in the upper epithelial layers, which might otherwise occur through activation of the ADPribosylation factor pathway. 7 Evidence suggests that several regulatory pathways must be subverted before host cells are transformed.…”

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confidence: 99%

Role and predictive strength of transglutaminase type 2 expression in premalignant lesions of the cervix

et al. 2011

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The demonstration that type 2 transglutaminase (TG2) can incorporate polyamine into the E7 oncoprotein of human papillomavirus (HPV) type 18 has led to the hypothesis that TG2 can have a role in the host cellular response to HPV infection. The aim of this study was to investigate whether HPV-related pathology, in infected human cervical epithelium, was associated with modulation of TG2 expression. Normal controls and HPVinfected cervical biopsies were analyzed for the expression of TG2, and the findings were compared with lesion grade. The correlation between TG2 expression and p16, a marker for HPV-induced dysplasia, and the retinoblastoma protein (Rb), a target of the E7 protein of HPV, was also investigated. Results obtained showed that TG2 was absent in normal squamous mucosa, whereas it was present in 100% CIN I lesions. Low-grade lesions showed significantly higher TG2 expression than high-grade lesions (Po0.0001). In 94% of CIN I more than 50% of the cells were positive for TG2, with a strong staining intensity ( þ 3), whereas a decreased staining intensity and a low number of positive cells were found in CIN II/III. In CIN I cases, both nuclear and cytoplasmic staining were found in cells exhibiting classical morphological features of HPV infection. In addition, during progression from low-grade squamous intraepithelial lesions to severe dysplasia, TG2 expression was inversely correlated with p16 (Pearson: À0.930), whereas a positive correlation was observed between the expression of TG2 and pRb (Pearson: 0.997). TG2 is expressed in HPV infection as an early phenomenon, not restricted to high-risk genotypes. TG2 upregulation is probably part of host cell reaction against HPV-induced tissue modification. It may act as a cellular antioxidant defense factor, playing an important role in counteracting oxidative damage in neoplastic disease.

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“…E6 degrades p53, whereas E7 is involved in deregulation of the Rb/E2F pathway (reviewed by Doorbar, 2006). Current literature indicates that the E7 protein exerts a more dominant role in transformation than E6 (Fiedler et al, 2004), although both oncoproteins contribute to malignant progression.…”

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confidence: 99%

The E7 protein from human papillomavirus type 16 enhances keratinocyte migration in an Akt-dependent manner

Charette

McCance

2007

Oncogene

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High level HPV‐16 E7 oncoprotein expression correlates with reduced pRb‐levels in cervical biopsies

Cited by 60 publications

References 63 publications

Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas

Human papillomavirus is frequently detected in gefitinib-responsive lung adenocarcinomas

Role and predictive strength of transglutaminase type 2 expression in premalignant lesions of the cervix

The E7 protein from human papillomavirus type 16 enhances keratinocyte migration in an Akt-dependent manner

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