K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation

Tamanaha-Nakasone, Ayumi; Uehara, Kanou; Tanabe, Yasuka; Ishikawa, Haruna; Yamakawa, Natsuko; Toyoda, Zensei; Kurima, Kiyoto; Kina, Shinichiro; Okubo, Yuko; Yamaguchi, Sayaka; Utsumi, Daisuke; Takahashi, Keiichi; Arakawa, Hirofumi; Arasaki, Akira; Kinjo, Takao

doi:10.1038/s41598-019-42763-0

Cited by 5 publications

(5 citation statements)

References 33 publications

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“…The procedure for retrovirus production and the construction of viral protein expressing MEFs have been described previously [ 16 ]. Briefly, the plasmids pMSCV- puro - 6E6 , pMSCV- puro - 11E6 , pMSCV- puro - 11E7 and pMSCV- neo - LMP-1 were transfected into packaging cell lines PT-67 (Clontech) using Lipofectamine 2000 (Thermo Fisher Scientific) and incubated for 48 h. Retroviruses harboring the various HPV and/or EBV genes were generated, and CF-1 cells were then infected with the viruses.…”

Section: Methodsmentioning

confidence: 99%

Co-expression of low-risk HPV E6/E7 and EBV LMP-1 leads to precancerous lesions by DNA damage

et al. 2021

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Background Low-risk human papillomavirus (HPV), such as types 6 and 11, is considered non-oncogenic, but these types have been detected in oral cancer tissue samples, suggesting their possible involvement in oral carcinogenesis. Because double infection of high-risk HPV and Epstein-Barr virus (EBV) is known to be involved in oral carcinogenesis, we hypothesized that low-risk HPV and EBV co-infection can transform the oral cells. To verify our hypothesis, we evaluated the transformation activity of cell lines expressing both low-risk HPV E6/E7 and EBV LMP-1. Methods We transduced HPV6, 11 and 16 E6/E7 genes and EBV LMP-1 gene into primary mouse embryonic fibroblasts. The cell lines were examined for indices of transformation activity such as proliferation, induction of DNA damage, resistance to apoptosis, anchorage-independent growth, and tumor formation in nude mice. To evaluate the signaling pathways involved in transformation, NF-κB and p53 activities were analyzed. We also assessed adhesion signaling molecules associated with anchorage-independent growth such as MMP-2, paxillin and Cat-1. Results Co-expression of low-risk HPV6 E6 and EBV LMP-1 showed increased cell proliferation, elevated NF-κB activity and reduced p53 induction. Moreover, co-expression of low-risk HPV6 E6 and EBV LMP-1 induced DNA damage, escaped from apoptosis under genotoxic condition and suppression of DNA damage response (DDR). Co-expression of low-risk HPV11 E6/E7 and EBV LMP-1 demonstrated similar results. However, it led to no malignant characteristics such as anchorage-independent growth, invasiveness and tumor formation in nude mice. Compared with the cells co-expressing high-risk HPV16 E6 and EBV LMP-1 that induce transformation, co-expression of low-risk HPV6 E6 and EBV LMP-1 was associated with low MMP-2, paxillin and Cat-1 expression. Conclusions The co-expression of low-risk HPV E6/E7 and EBV LMP-1 does not induce malignant transformation, but it allows accumulation of somatic mutations secondary to increased DNA damage and suppression of DDR. Thus, double infection of low-risk HPV and EBV could lead to precancerous lesions.

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Section: Methodsmentioning

confidence: 99%

Co-expression of low-risk HPV E6/E7 and EBV LMP-1 leads to precancerous lesions by DNA damage

et al. 2021

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“…ORF K1 measures approximately 1080 bp [46] (Table 1). The K1 transmembrane protein is an oncoprotein [64] encoded by this gene, described in 1998 by Lee et al [65]. K1 is 279 amino acids in length [46] and is primarily expressed during KSHV lytic replication [66].…”

Section: Orf K1 (K1)mentioning

confidence: 99%

“…In addition, K1 transgenic mice develop spindle cell sarcomatoid tumors and plasmablastic lymphoma, thought to be mediated by the activation of NF-κB and the B-cell transcription factor, Oct2 [70,71]. K1 is thought to be involved in the activation of tyrosine immunoreceptors that also activate a cascade linked to the tumorigenesis of KS [64].…”

Section: Orf K1 (K1)mentioning

confidence: 99%

Human Gammaherpesvirus 8 Oncogenes Associated with Kaposi’s Sarcoma

Lopes

Marinho

Medeiros

et al. 2022

IJMS

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Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human gammaherpesvirus 8 (HHV-8), contains oncogenes and proteins that modulate various cellular functions, including proliferation, differentiation, survival, and apoptosis, and is integral to KSHV infection and oncogenicity. In this review, we describe the most important KSHV genes [ORF 73 (LANA), ORF 72 (vCyclin), ORF 71 or ORFK13 (vFLIP), ORF 74 (vGPCR), ORF 16 (vBcl-2), ORF K2 (vIL-6), ORF K9 (vIRF 1)/ORF K10.5, ORF K10.6 (vIRF 3), ORF K1 (K1), ORF K15 (K15), and ORF 36 (vPK)] that have the potential to induce malignant phenotypic characteristics of Kaposi’s sarcoma. These oncogenes can be explored in prospective studies as future therapeutic targets of Kaposi’s sarcoma.

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“…On the other hand, a study has shown in vitro that the K1 gene in the epidemic form was associated with a higher transforming activity compared with those in the classic form. This higher activity was also correlated with the severity of the clinical presentation [ 136 ].…”

Section: Epidemiologymentioning

confidence: 99%

Kaposi’s Sarcoma-Associated Herpesvirus, the Etiological Agent of All Epidemiological Forms of Kaposi’s Sarcoma

Jary

Veyri

Gothland

et al. 2021

Cancers

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Kaposi’s sarcoma-associated herpesvirus (KSHV), also called human herpesvirus 8 (HHV-8), is an oncogenic virus belonging to the Herpesviridae family. The viral particle is composed of a double-stranded DNA harboring 90 open reading frames, incorporated in an icosahedral capsid and enveloped. The viral cycle is divided in the following two states: a short lytic phase, and a latency phase that leads to a persistent infection in target cells and the expression of a small number of genes, including LANA-1, v-FLIP and v-cyclin. The seroprevalence and risk factors of infection differ around the world, and saliva seems to play a major role in viral transmission. KSHV is found in all epidemiological forms of Kaposi’s sarcoma including classic, endemic, iatrogenic, epidemic and non-epidemic forms. In a Kaposi’s sarcoma lesion, KSHV is mainly in a latent state; however, a small proportion of viral particles (<5%) are in a replicative state and are reported to be potentially involved in the proliferation of neighboring cells, suggesting they have crucial roles in the process of tumorigenesis. KSHV encodes oncogenic proteins (LANA-1, v-FLIP, v-cyclin, v-GPCR, v-IL6, v-CCL, v-MIP, v-IRF, etc.) that can modulate cellular pathways in order to induce the characteristics found in all cancer, including the inhibition of apoptosis, cells’ proliferation stimulation, angiogenesis, inflammation and immune escape, and, therefore, are involved in the development of Kaposi’s sarcoma.

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K1 gene transformation activities in AIDS-related and classic type Kaposi’s sarcoma: Correlation with clinical presentation

Cited by 5 publications

References 33 publications

Co-expression of low-risk HPV E6/E7 and EBV LMP-1 leads to precancerous lesions by DNA damage

Co-expression of low-risk HPV E6/E7 and EBV LMP-1 leads to precancerous lesions by DNA damage

Human Gammaherpesvirus 8 Oncogenes Associated with Kaposi’s Sarcoma

Kaposi’s Sarcoma-Associated Herpesvirus, the Etiological Agent of All Epidemiological Forms of Kaposi’s Sarcoma

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