Adeno-Associated Virus Is Associated with a Lower Risk of High-Grade Cervical Neoplasia

Coker, Ann L.; Russell, Robert B.; Bond, Sharon; Pirisi, Lucia; Liu, Yong; Mane, Michael; Kokorina, Natalia A.; Gerasimova, Tsilya; Hermonat, Paul L.

doi:10.1006/exmp.2000.2347

Cited by 33 publications

(23 citation statements)

References 40 publications

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“…For a cancer therapy, wild-type AAV-2 offers some unique properties. Next to a direct antioncogenic effect of wt-AAV, 18,19 infection with wt-AAV-2-prevented chemotherapy-related toxic side effects 20 and mediated sensitivity to chemotherapy. 21,22 Moreover, infection and gene expression occur in both nondividing and dividing cells.…”

Section: Discussionmentioning

confidence: 99%

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

et al. 2003

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In this study, we elucidated the potential of recombinant adeno-associated virus type-2 (rAAV-2) vectors for lung cancer gene therapy. Cell lines of the three major histological subtypes of non-small cell lung cancer (NSCLC) were highly susceptible for rAAV-2 showing transduction rates between 63.4 and 98.9%. In contrast, cell lines of small cell carcinomas were resistant to rAAV-2 infection. For restoration of p53 function in p53 deficient NSCLC, a rAAV-2 vector was constructed containing wt p53 cDNA. Following transduction with rAAV-p53, cell growth of all NSCLC cell lines was significantly reduced in a dose-dependent manner between 44 and 71.7% in comparison with rAAV-GFP transduced cells. The reduction of tumor cell growth was associated with increased apoptosis. Adding cisplatin to rAAV-p53-infected cells led to a significant growth inhibition between 81 and 91% indicating a synergistic effect between cisplatin and rAAV-p53. Interestingly, the tumor cells surviving cisplatin and rAAV-p53 treatment were inhibited in their ability to form colonies as reflected by a reduction of colony growth between 57 and 90.4%. In conclusion, rAAV-2 vectors exhibit a strong tropism for NSCLC. Successful inhibition of tumor cell growth following transduction with a rAAV-p53 vector underlines the potential role of rAAV-2 in cancer gene therapy.

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Section: Discussionmentioning

confidence: 99%

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

et al. 2003

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“…Coinfection with adeno-associated virus is associated with a significantly reduced risk of cervical neoplasia (26). Adenoassociated virus replication gene product Rep78 disrupts the transcription of the HPV-16 E6 and E7 oncogenes by interfering with the binding of the TATA binding protein to the p97 core promoter in the LCR region of the HPV genome (110).…”

Section: Epidemiologymentioning

confidence: 99%

Human papillomavirus and cervical cancer

2000

Reproductive Health Matters

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“…Seroepidemiological studies have demonstrated that women with HPV-associated cervical carcinoma have antibodies to AAV less frequently compared to matched controls (27,46,68,71). More recent epidemiological studies have also suggested that the presence of AAV DNA in cervical tissue (19) and AAV2 seropositivity (68) are associated with a reduced risk of developing high-grade cervical squamous intraepithelial lesions. Thus, AAV has been proposed to antagonize the development of HPV-related carcinoma (45,62).…”

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confidence: 99%

Adeno-Associated Virus Type 2 Increases Proteosome-Dependent Degradation of p21^WAF1in a Human Papillomavirus Type 31b-Positive Cervical Carcinoma Line

Alam

Sen

Brashear

et al. 2006

J Virol

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Adeno-associated virus type 2 (AAV2) seropositivity is negatively correlated with the development of human papillomavirus (HPV)-associated cervical cancer. We have begun analysis of the molecular mechanisms underlying AAV2-mediated oncosuppression through cell cycle regulation in HPV-infected keratinocytes isolated from a low-grade cervical lesion. AAV2 superinfection of HPV type 31b (HPV31b)-positive cells at early times postinfection resulted in degradation of the cyclin-dependent kinase (CDK) inhibitor p21 WAF1 protein in a proteosome-dependent manner. Downstream consequences of lowering p21 WAF1 levels included a proportional loss of cyclin E/CDK2 complexes bound to p21 WAF1 . The loss of stable p21 WAF1 /cyclin E/CDK2 complexes coincided with an increase in CDK2-associated kinase activity and cyclin E levels. Both events have the potential to enhance the G 1 /S transition point mediated by active cyclin E/CDK2 complexes. Concurrently, cyclin A and E2F levels were decreased, conditions reminiscent of delayed entrance into the S phase of the cell cycle. On the other hand, infection of primary human foreskin keratinocytes with AAV2 resulted in upregulation of p21 WAF1 protein levels, reminiscent of a block in G 1 phase progression. We propose that by downregulating p21 WAF1 , AAV2 initiates cell cycle activities leading to enhanced G 1 /S phase-like conditions which may be favorable for AAV2-specific functions and may lead to downstream interference with HPV-associated cervical cancer progression.Infection of the mucosal epithelium of the anogenital region by high-risk human papillomavirus (HPV) types is positively associated with the development and neoplastic progression of cervical carcinoma (12,44,83,84). Specifically, high-risk HPV types 16, 18, 31, 33, and 45 are associated with over 95% of all cervical cancers (28,81,85). The tumorigenicity of HPV has been attributed to the E6 and E7 oncogenes, which interfere with the functions of cellular tumor suppressors p53 (61) and pRb (14, 42), respectively. Both oncoproteins are involved in the release of the G 1 cell cycle block in differentiating keratinocytes, thus deregulating key cell cycle checkpoints and promoting viral DNA replication (25). On the other hand, infection with the adenoassociated virus type 2 (AAV2), a helper-dependent human parvovirus, may have a negative effect against the development of cervical cancer (46). Seroepidemiological studies have demonstrated that women with HPV-associated cervical carcinoma have antibodies to AAV less frequently compared to matched controls (27,46,68,71). More recent epidemiological studies have also suggested that the presence of AAV DNA in cervical tissue (19) and AAV2 seropositivity (68) are associated with a reduced risk of developing high-grade cervical squamous intraepithelial lesions. Thus, AAV has been proposed to antagonize the development of HPV-related carcinoma (45,62).The antiproliferative and tumor-suppressive properties of AAV have been suggested to result from its ability to target oncogenic v...

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Adeno-Associated Virus Is Associated with a Lower Risk of High-Grade Cervical Neoplasia

Cited by 33 publications

References 40 publications

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

Human papillomavirus and cervical cancer

Adeno-Associated Virus Type 2 Increases Proteosome-Dependent Degradation of p21^WAF1in a Human Papillomavirus Type 31b-Positive Cervical Carcinoma Line

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Adeno-Associated Virus Is Associated with a Lower Risk of High-Grade Cervical Neoplasia

Cited by 33 publications

References 40 publications

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

Non-small lung cancer cells are prime targets for p53 gene transfer mediated by a recombinant adeno-associated virus type-2 vector

Human papillomavirus and cervical cancer

Adeno-Associated Virus Type 2 Increases Proteosome-Dependent Degradation of p21WAF1in a Human Papillomavirus Type 31b-Positive Cervical Carcinoma Line

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Adeno-Associated Virus Type 2 Increases Proteosome-Dependent Degradation of p21^WAF1in a Human Papillomavirus Type 31b-Positive Cervical Carcinoma Line