High Prevalence of Human Cytomegalovirus in Prostatic Intraepithelial Neoplasia and Prostatic Carcinoma

Samanta, Minu; Harkins, Lualhati; Klemm, Katrin; Britt, William J.; Cobbs, Charles S.

doi:10.1097/01.ju.0000080263.46164.97

Cited by 275 publications

(208 citation statements)

References 13 publications

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“…[14][15][16][17] In addition, CMV infection has been shown to stimulate nucleic acid and protein synthesis, activate transcription of protooncogenes, and modulate expression of proteins involved in cellular regulatory and apoptotic pathways. [14][15][16][17][24][25][26][27] CMV has been associated with several specific human malignancies including carcinomas of the cervix, [28][29][30][31][32] prostate, [33][34][35][36] and colon. [37][38][39] However, a number of conflicting reports have either failed to show evidence of an association with CMV or have questioned the significance of the presence of CMV in these particular tumors.…”

Section: Discussionmentioning

confidence: 99%

Lack of association of cytomegalovirus with human brain tumors

et al. 2005

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Cytomegalovirus (CMV) is thought to possess oncogenic properties and has been linked with a number of human malignancies. CMV infection was recently described in association with malignant gliomas. The intent of the present study was to further investigate the reported association between CMV and malignant gliomas. Tissue from 22 brain tumors of various histologic types and grades, four normal brains, six breast carcinomas, six colon carcinomas, six lung carcinomas, and six sarcomas were evaluated for the presence of CMV by polymerase chain reaction (PCR), in situ hybridization, and immunohistochemical methods. None of the brain tumors or normal brain tissue tested demonstrated evidence of CMV pp65 or early nuclear proteins by immunohistochemistry. In addition, no CMV RNA or DNA was detected in these cases by in situ hybridization and PCR. None of the carcinomas or sarcomas evaluated were positive for CMV by immunohistochemistry, in situ hybridization, or PCR. The findings of the present study suggest that CMV is not significantly associated with brain tumors in humans.

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Section: Discussionmentioning

confidence: 99%

Lack of association of cytomegalovirus with human brain tumors

et al. 2005

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“…However, except for non-Hodgkin's lymphoma, the incidence of primary CNS tumours is not increased in immunosuppressed patients. Moreover, despite recent investigations demonstrating the presence of HCMV in prostate and colorectal cancers Samanta et al, 2003), as yet this virus is not recognised as an oncogenic factor, at least in vivo.…”

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confidence: 94%

Detection of human cytomegalovirus genome and gene products in central nervous system tumours

et al. 2005

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Human cytomegalovirus (HCMV) genome and related proteins have been reported in a great proportion of malignant gliomas. However, these results are unexpected since HCMV is not known as an oncogenic virus. By immunohistochemistry (with an anti-IE1 monoclonal antibody) and in situ hybridisation (with biotinylated DNA probes) on tissue microarrays and frozen sections, we investigated a French series of central nervous system (CNS) tumours, including 97 glioblastomas. In 10 cases of glioblastoma, rare astrocyte-like cells, admixed with tumour cells, stained positively for HCMV and in one case a doubtful staining of rare cells was noticed. This may indicate a reactivation of the virus under local immunosuppression but none of the cases of CNS tumours (n ¼ 132) contained HCMV genomes and/or proteins in a significant proportion of tumour cells. Our results strongly suggest that HCMV is unlikely to be implicated in the development of human malignant gliomas, at least in French cases.

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“…Persistent CMV infection can enhance the tumorigenic and invasive properties of human neuroblastoma cells in culture (Hoever et al, 2005), while reducing their propensity to undergo apoptosis (Terrasson et al, 2005). According to one group, CMV genes or proteins are expressed in some tumors, for instance in colon (Harkins et al, 2002) and prostate carcinoma (Samanta et al, 2003), but at present it is not yet clear if CMV exerts any co-oncogenic effects (Froberg, 2004).…”

Section: Introductionmentioning

confidence: 99%

Structure–function analysis of the interaction between Bax and the cytomegalovirus-encoded protein vMIA

et al. 2007

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The viral mitochondrial inhibitor of apoptosis (vMIA) encoded by the human cytomegalovirus exerts cytopathic effects and neutralizes the proapoptotic endogenous Bcl-2 family member Bax by recruiting it to mitochondria, inducing its oligomerization and membrane insertion. Using a combination of computational modeling and mutational analyses, we addressed the structure-function relationship of the molecular interaction between the protein Bax and the viral antiapoptotic protein vMIA. We propose a model in which vMIA exhibits an overall fold similar to Bcl-X L . In contrast to Bcl-X L , however, this predicted conformation of vMIA does not bind to the BH3 domain of Bax and rather engages in electrostatic interactions that involve a stretch of amino acids between the BH3 and BH2 domains of Bax and an a-helical domain located within the previously defined Bax-binding domain of vMIA, between the putative BH1-like and BH2-like domains. According to this model, vMIA is likely to bind Bax preferentially in its membraneinserted conformation. The capacity of vMIA to cause fragmentation of the mitochondrial network and disorganization of the actin cytoskeleton is independent of its Baxbinding function. We found that D131-147 vMIA mutant, which lacks both the Bax-binding function and cell-death suppression but has intact mitochondria-targeting capacity, is similar to vMIA in its ability to disrupt the mitochondrial network and to disorganize the actin cytoskeleton. vMIAD131-147 is a dominant-negative inhibitor of the antiapoptotic function of wild-type vMIA. Our experiments with vMIAD131-147 suggest that vMIA forms homooligomers, which may engage in cooperative and/or multivalent interactions with Bax, leading to its functional neutralization.

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High Prevalence of Human Cytomegalovirus in Prostatic Intraepithelial Neoplasia and Prostatic Carcinoma

Abstract: To our knowledge these data demonstrate for the first time the specific localization of HCMV nucleic acids and proteins in a high percent of PIN and prostate carcinoma lesions, and raise the possibility that HCMV might contribute to the natural history of prostatic cancer.

Cited by 275 publications

References 13 publications

Lack of association of cytomegalovirus with human brain tumors

Lack of association of cytomegalovirus with human brain tumors

Detection of human cytomegalovirus genome and gene products in central nervous system tumours

Structure–function analysis of the interaction between Bax and the cytomegalovirus-encoded protein vMIA

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