Retrovirus-like particles released from the human breast cancer cell line T47-D display type B- and C-related endogenous retroviral sequences

Seifarth, Wolfgang; Skladny, Heyko; Krieg-Schneider, F.; Reichert, Anja; Hehlmann, Rüdiger; Leib-Mösch, Christine

doi:10.1128/jvi.69.10.6408-6416.1995

Cited by 87 publications

(33 citation statements)

References 53 publications

(59 reference statements)

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“…33 Several groups followed with reports of HML-2 mRNA and viral particle expression in breast cancer. 29,[34][35][36] Wang-Johanning et al refined this work to produce data that accurately quantified HML-2 env transcripts and spliced transcripts in breast tumors demonstrating elevated levels Figure 1. Structure of HERV-K provirus.…”

Section: Herv-k and Solid Tumorsmentioning

confidence: 99%

Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice?

et al. 2014

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Harbored as relics of ancient germline infections, human endogenous retroviruses (HERVs) now constitute up to 8% of our genome. A proportion of this sequence has been co-opted for molecular and cellular processes, beneficial to human physiology, such as the fusogenic activity of the envelope protein, a vital component of placentogenesis. However, the discovery of high levels of HERV-K mRNA and protein and even virions in a wide array of cancers has revealed that HERV-K may be playing a more sinister role–a role as an etiological agent in cancer itself. Whether the presence of this retroviral material is simply an epiphenomenon, or an actual causative factor, is a hotly debated topic. This review will summarize the current state of knowledge regarding HERV-K and cancer and attempt to outline the potential mechanisms by which HERV-K could be involved in the onset and promotion of carcinogenesis.

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Section: Herv-k and Solid Tumorsmentioning

confidence: 99%

Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice?

et al. 2014

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“…Purified particles had functional RT and particle cDNA hybridized strongly to human genomic DNA but not to mouse or cat DNA. Recently, the same group, Seifarth et al (1995), amplified three different ERV sequences from purified T47D particles using RT-PCR with degenerate primers from a conserved region of the pol gene. One of the ERV sequences had 65% identity with the RT region of HERV-KIO, whereas another two were defective type C-related ERVs.…”

Section: Erv Particle Formationmentioning

confidence: 99%

The Potential Roles of Endogenous Retroviruses in Autoimmunity

Nakagawa

Harrison²

1996

Immunological Reviews

114

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Endogenous retroviruses (ERVs) are estimated to comprise up to 1% of human DNA. While the genome of many ERVs is interrupted by termination codons, deletions or frame shift mutations, some ERVs are transcriptionally active and recent studies reveal protein expression or particle formation by human ERVs. ERVs have been implicated as aetiological agents of autoimmune disease, because of their structural and sequence similarities to exogenous retroviruses associated with immune dysregulation and their tissue-specific or differentiation-dependent expression. In fact, retrovirus-like particles distinct from those of known exogenous retroviruses and immune responses to ERV proteins have been observed in autoimmune disease. Quantitatively or structurally aberrant expression of normally cryptic ERVs, induced by environmental or endogenous factors, could initiate autoimmunity through direct or indirect mechanisms. ERVs may lead to immune dysregulation as insertional mutagens or cis-regulatory elements of cellular genes involved in immune function. ERVs may also encode elements like tax in human T-lymphotrophic virus type I (HTLV-I) or tat in human immunodeficiency virus-I (HIV-I) that are capable of transactivating cellular genes. More directly, human ERV gene products themselves may be immunologically active, by analogy with the superantigen activity in the long terminal repeat (LTR) of mouse mammary tumour viruses (MMTV) and the non-specific immunosuppressive activity in mammalian type C retrovirus env protein. Alternatively, increased expression of an ERV protein, or expression of a novel ERV protein not expressed in the thymus during acquisition of immune tolerance, may lead to its perception as a neoantigen. Paraneoplastic syndromes raise the possibility that novel ERV-encoded epitopes expressed by a tumour elicit immunity to cross-reactive epitopes in normal tissues. Recombination events between different but related ERVs, to whose products the host is immunologically tolerant, may also generate new antigenic determinants. Frequently reported humoral immunity to exogenous retrovirus proteins in autoimmune disease could be elicited by cross-reactive ERV proteins. A review of the evidence implicating ERVs in immune dysfunction leads to the conclusion that direct molecular studies are likely to establish a pathogenic role for ERVs in autoimmune disease.

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“…It has been shown that HERV transcription is increased in several human cancers 7,8 and in breast cancer cell lines. 9,10 We have found that expression of one HERV group, HERV-K(HML-2), is increased in breast cancer. [11][12][13][14] The HML-2 group includes the most recently active retroviruses, and a comprehensive analysis of HML-2 element distribution within the human genome has recently been reported.…”

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confidence: 99%

Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early‐stage breast cancer

Wang-Johanning

Esteva

et al. 2013

Intl Journal of Cancer

106

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A simple and accurate test to detect early-stage breast cancer has not been developed. Previous studies indicate that the level of human endogenous retrovirus type K (group HERV-K(HML-2)) transcription may be increased in human breast tumors. We hypothesized that HERV-K(HML-2) reactivation can serve as a biomarker for early detection of breast cancer. Serum samples were collected from women without cancer (controls) and patients with ductal carcinoma in situ (DCIS) and invasive breast cancer. ELISA assays were employed to detect serum anti-HERV-K(HML-2) antibody titers. RNA was extracted from sera and analyzed by real-time RT-PCR to quantitate the level of HERV-K(HML-2) mRNA. We measured significantly higher serum mRNA and serum antibody titers against HERV-K(HML-2) proteins in women with DCIS and stage I disease than in women without cancer. At optimized cutoffs for the antibody titers, the assay produced an area under the ROC curve (AUC) of 0.89 (95% confidence interval 0.77 to 1.00) for DCIS and of 0.95 (95% confidence interval 0.89 to 1.00) for invasive breast cancer. These AUCs are comparable to those observed for mammograms. We also found that serum HERV-K(HML-2) mRNA tended to be higher in breast cancer patients with a primary tumor who later on developed the metastatic disease than in patients who did not develop cancer metastasis. Our results show that HERV-K(HML-2) antibodies and mRNA are already elevated in the blood at an early stage of breast cancer, and further increase in patients who are at risk of developing a metastatic disease.

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Retrovirus-like particles released from the human breast cancer cell line T47-D display type B- and C-related endogenous retroviral sequences

Abstract: The human mammary carcinoma cell line T47-D releases retrovirus-like particles of type B morphology in a steroid-dependent manner (I.

Cited by 87 publications

References 53 publications

Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice?

Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice?

The Potential Roles of Endogenous Retroviruses in Autoimmunity

Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early‐stage breast cancer

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