Eucarotic expression of the ENV protein of the human endogenous retrovirus-K10 (HERV-K10) and the detection of antibodies in patients with testicular tumors

The genomes of vertebrates contain sequences that are similar to present-day exogenous retroviruses. Such sequences, called endogenous retroviruses (ERVs), have resulted from ancestral germ line infections by exogenous retroviruses which have thereafter been transmitted in a Mendelian fashion. By analogy to exogenous tumorigenic retroviruses, ERVs have been implicated in the pathogenesis of cancer. Cumulative evidence from animal models indicates that ERVs may participate in the process of malignant transformation or promote tumor growth, e.g. through insertional mutagenesis or via counteracting tumor immunosurveillance. Here, we review the role of ERVs in tumorigenesis with focus on human ERVs (HERVs) in human cancer. Although available data suggest a potential role of HERVs in human cancers, in particular germ cell tumors, the contributions of HERVs to human tumorigenesis warrant further elucidation. (Part of a multi-author review).

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“…Germ cell tumor tissue HERV-K(HML-2) Gag [106] Germ cell tumor cell lines (GH, Tera-1, NCCIT, 2102Ep)…”

Section: Tumor Type Herv Protein* Referencesmentioning

confidence: 99%

“…HERV-K(HML-2) Gag HERV-K (HML-2) Env HERV-K(HML-2) Rec HERV-K(HML-2) Np9 [106] [120] [121,131] [126]…”

Section: Tumor Type Herv Protein* Referencesmentioning

confidence: 99%

Endogenous retroviruses

Ruprecht

Mayer

Sauter

et al. 2008

Cell. Mol. Life Sci.

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136

155

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“…Classic seminomas originate from developmentally early arising, immature and differentiation-defective carcinoma in situ (CIS) cells. Since patients with GCT produce antibodies against HERV proteins and since GCT cells express splice variants of the HERV env transcript, of which one is translated into the Rec protein (Lower et al, 1995;Herbst et al, 1996;Sauter et al, 1996;Magin et al, 1999;Yang et al, 1999), we asked whether Rec, inducibly expressed in all tissues of transgenic mice, can induce organ-specific changes indicative of a disturbance of germ cell maturation or the development of CIS.…”

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confidence: 99%

Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors

et al. 2005

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Germ cell tumors (GCTs) are among the most common malignancies in young men. We have previously documented that patients with GCT frequently produce serum antibodies directed against proteins encoded by human endogenous retrovirus (HERV) type K sequences. Transcripts originating from the env gene of HERV-K, including the rec-relative of human immunodeficiency virus rev, are highly expressed in GCTs. We report here that mice that inducibly express HERV-K rec show a disturbed germ cell development and may exhibit, by 19 months of age, changes reminiscent of carcinoma in situ, the predecessor lesion of classic seminoma in humans. This provides the first direct evidence that the expression of a human endogenous retroviral gene previously established as a marker in human germ cell tumors may contribute to organ-specific tumorigenesis in a transgenic mouse model.

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“…The detection of further characteristics and functions of cORF, besides HERV‐K RNA export, is of particular interest because of recent evidence that (i) HERV‐K expression is associated with GCTs [13], (ii) cORF has the capacity to transform cells, and (iii) cORF interacts with PLZF [14]. PLZF is involved in functions such as cell differentiation and testis development [16,17], suggesting that deregulation of PLZF, possibly by cORF, might contribute to germ‐cell transformation.…”

Section: Resultsmentioning

confidence: 99%

The Rev/Rex homolog HERV‐K cORF multimerizes via a C‐terminal domain

Boese¹,

Galli²,

Geyer

et al. 2001

FEBS Letters

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Expression of human endogenous retrovirus K (HERV-K) is associated with germ-cell neoplasia. HERV-K encodes a protein of the Rev/Rex family, cORF, that supports cellular transformation and binds the promyelocytic leukemia zinc finger (PLZF) protein implicated in spermatogenesis. Rev/ Rex function invariably depends on multimerization. Here we show that cORF likewise self-associates to form higher-order oligomers. Amino acids (aa) 47^87 in cORF are sufficient, aa 75^87 essential for self-association. Consistently, this domain is predicted to form a hydrophobic K K-helix that may represent an oligomerization interface. The existence of a dimerizationcompetent cORF mutant lacking PLZF-binding activity (cORF47^87) suggests a way of dominant negative inhibition of the proposed tumor susceptibility factor cORF. ß

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Eucarotic expression of the ENV protein of the human endogenous retrovirus-K10 (HERV-K10) and the detection of antibodies in patients with testicular tumors

Cited by 9 publications

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Endogenous retroviruses

Endogenous retroviruses

Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors

The Rev/Rex homolog HERV‐K cORF multimerizes via a C‐terminal domain

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