BK polyomavirus infection promotes growth and aggressiveness in bladder cancer

Zeng, Yanwu; Sun, Jiajia; Bao, Juan Francisco Gibaja; Zhu, Tongyu

doi:10.1186/s12985-020-01399-7

Cited by 17 publications

(12 citation statements)

References 30 publications

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“…The association between human polyomaviruses and bladder carcinoma continues to be controversial. While some studies suggested an association between BKPyV and JCPyV infections and bladder carcinoma [ 17 – 19 ], the other studies denied this association [ 3 , 20 – 22 ]. These studies have been performed in different populations with different environmental risk factors and genetic backgrounds and have failed to reach a consensus.…”

Section: Discussionmentioning

confidence: 99%

BK and JC polyomaviruses and risk of urothelial bladder carcinoma: a preliminary study in the northern shores of Persian Gulf, Iran

Taherkhani

Farshadpour

2022

Infect Agents Cancer

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Background Bladder cancer is a challenging public health concern in South of Iran because of its high prevalence and the related medical expenses. Although the exact etiology of bladder cancer remains unknown, given the cell transforming ability and oncogenic potential of the members of Polyomaviridae families, this study was conducted to evaluate the magnitude of BK polyomavirus (BKPyV) and John Cunningham polyomavirus (JCPyV) among patients with bladder cancer residents in the northern shores of the Persian Gulf, South of Iran. Methods Totally 211 patients with bladder cancer were enrolled in this study. Bladder biopsy samples of these patients and patients with interstitial cystitis as well as autoptic samples of healthy bladder were tested for detection of BKPyV and JCPyV by semi-nested PCR–RFLP followed by sequencing. Results BKPyV and JCPyV were detected in 1.7% and 6.1% of bladder cancer samples, respectively. These samples were infected with JCPyV genotypes 2, 3 and 6 and BKPyV genotypes I and IV. BKPyV and JCPyV coinfection was detected in 2 samples. Moreover, one of the healthy bladder samples was positive for BKPyV, and one of the interstitial cystitis samples was positive for JCPyV. Although the majority of infected patients were in the age group 70–79 years, male, residents in Tangestan, stage Ta–T1, and low-grade and high-grade papillary urothelial carcinoma, the prevalence of BKPyV and JCPyV among patients with bladder cancer was not statistically associated with age, gender, place of residency, and stage and grade of the tumor. Conclusion Despite identifying BKPyV and JCPyV in a number of bladder cancer biopsy specimens and the high prevalence of bladder cancer among people resident in South of Iran, it is suggested that these viruses are unlikely to be effective causative factors in bladder carcinogenesis in this region. Therefore, environmental risk factors and genetic backgrounds may have a more prominent role than human polyomaviruses in the development of bladder cancer in South of Iran.

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Section: Discussionmentioning

confidence: 99%

BK and JC polyomaviruses and risk of urothelial bladder carcinoma: a preliminary study in the northern shores of Persian Gulf, Iran

Taherkhani

Farshadpour

2022

Infect Agents Cancer

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“…More recently, the discovery of the novel Merkel cell Polyomavirus (MCPyV) and its clear role in the pathogenesis of Merkel cell carcinomas [ 62 ] opened new insights into the oncogenicity of polyomaviruses in humans. Now the role of JCPyV and specifically of the oncoprotein T-Antigen have been demonstrated also in colon carcinomas [ 9 , 55 , 63 ], and another notorious human polyomavirus, BKPyV has been recently implicated in the oncogenesis of urothelial and bladder carcinomas [ 64 , 65 , 66 ]. This animal model has also yielded valuable data to elucidate the different oncogenic pathways affected by T-Antigen.…”

Section: Discussionmentioning

confidence: 99%

Induction of Brain Tumors by the Archetype Strain of Human Neurotropic JCPyV in a Transgenic Mouse Model

Valle

Khalili

2021

Viruses

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JC Virus (JCPyV), a member of the Polyomaviridiæ family, is a human neurotropic virus with world-wide distribution. JCPyV is the established opportunistic infectious agent of progressive multifocal leukoencephalopathy, a fatal demyelinating disease, which results from the cytolytic infection of oligodendrocytes. Mutations in the regulatory region of JCPyV determine the different viral strains. Mad-1 the strain associated with PML contains two 98 base pair repeats, whereas the archetype strain (CY), which is the transmissible form of JCPyV, contains only one 98 tandem with two insertions of 62 and 23 base pairs respectively. The oncogenicity of JCPyV has been suspected since direct inoculation into the brain of rodents and primates resulted in the development of brain tumors and has been attributed to the viral protein, T-Antigen. To further understand the oncogenicity of JCPyV, a transgenic mouse colony containing the early region of the archetype strain (CY), under the regulation of its own promoter was generated. These transgenic animals developed tumors of neural crest origin, including: primitive neuroectodermal tumors, medulloblastomas, adrenal neuroblastomas, pituitary tumors, malignant peripheral nerve sheath tumors, and glioblastomas. Neoplastic cells from all different phenotypes express T-Antigen. The close parallels between the tumors developed by these transgenic animals and human CNS tumors make this animal model an excellent tool for the study of viral oncogenesis.

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“…This suggests a role of JCPyV in colorectal malignancy through activation of the Wnt pathway, although JCPyV detection is frequent in both normal colorectal and colorectal cancer tissues [ (Shavaleh et al, 2020;Shoraka et al, 2020); Supplementary Table 1]. Infection of human bladder cancer cells with BKPyV activated the β-catenin signaling pathway, but an interaction between LT-ag and β-catenin was not investigated (Zeng et al, 2020). Ectopic expression of SV40 sT-ag in HEK293 upregulated several genes encoding proteins involved in the Wnt signaling (Ali-Seyed et al, 2006).…”

Section: Novel Human Polyomaviruses and The Wnt Pathwaymentioning

confidence: 99%

Functional Domains of the Early Proteins and Experimental and Epidemiological Studies Suggest a Role for the Novel Human Polyomaviruses in Cancer

2022

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As their name indicates, polyomaviruses (PyVs) can induce tumors. Mouse PyV, hamster PyV and raccoon PyV have been shown to cause tumors in their natural host. During the last 30 years, 15 PyVs have been isolated from humans. From these, Merkel cell PyV is classified as a Group 2A carcinogenic pathogen (probably carcinogenic to humans), whereas BKPyV and JCPyV are class 2B (possibly carcinogenic to humans) by the International Agency for Research on Cancer. Although the other PyVs recently detected in humans (referred to here as novel HPyV; nHPyV) share many common features with PyVs, including the viral oncoproteins large tumor antigen and small tumor antigen, as their role in cancer is questioned. This review discusses whether the nHPyVs may play a role in cancer based on predicted and experimentally proven functions of their early proteins in oncogenic processes. The functional domains that mediate the oncogenic properties of early proteins of known PyVs, that can cause cancer in their natural host or animal models, have been well characterized and we examined whether these functional domains are conserved in the early proteins of the nHPyVs and presented experimental evidence that these conserved domains are functional. Furthermore, we reviewed the literature describing the detection of nHPyV in human tumors.

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BK polyomavirus infection promotes growth and aggressiveness in bladder cancer

Cited by 17 publications

References 30 publications

BK and JC polyomaviruses and risk of urothelial bladder carcinoma: a preliminary study in the northern shores of Persian Gulf, Iran

BK and JC polyomaviruses and risk of urothelial bladder carcinoma: a preliminary study in the northern shores of Persian Gulf, Iran

Induction of Brain Tumors by the Archetype Strain of Human Neurotropic JCPyV in a Transgenic Mouse Model

Functional Domains of the Early Proteins and Experimental and Epidemiological Studies Suggest a Role for the Novel Human Polyomaviruses in Cancer

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