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

Galli, Uwe M; Sauter, Marlies; Lecher, Bernd; Maurer, Simone; Herbst, Hermann; Roemer, Klaus; Mueller-Lantzsch, Nikolaus

doi:10.1038/sj.onc.1208543

Cited by 120Testicular diseases and treatmentsChromosomal and Genetic VariationsSperm and Testicular Function

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

Galli, Uwe M, Sauter, Marlies, Lecher, Bernd, Maurer, Simone, Herbst, Hermann, Roemer, Klaus, Mueller-Lantzsch, Nikolaus·2005·Oncogene

DOI 10.1038/sj.onc.1208543

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Abstract

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 Rec protein produced by the HERV-K(HML2) rec gene, when expressed as a transgene in mice, interferes with germ cell development and causes lesions that resemble carcinoma.
“For example, the Rec protein produced by the HERV-K(HML2) rec gene, an alternative splicing product of the HERV-K(HML2) env gene (Fig. 3), when expressed as a transgene in mice, interferes with germ cell development and causes lesions that resemble carcinoma 64.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [64]

Regulation of Cell Fate Decision of Undifferentiated Spermatogonia by GDNF
Meng, X., Lindahl, M., Hyvönen, M. E., Parvinen, M., de Rooij, D. G., Hess, M. W., Raatikainen-Ahokas, A., Sainio, K., Rauvala, H., Lakso, M., et al. (2000) · Science · doi:10.1126/science.287.5457.1489 · Cited by 1,404 · see citing works
Essential role of Plzf in maintenance of spermatogonial stem cells
Costoya, J. A., Hobbs, R. M., Barna, M., Cattoretti, G., Manova, K., Sukhwani, M., Orwig, K. E., Wolgemuth, D. J., & Pandolfi, P. P. (2004) · Nature Genetics · doi:10.1038/ng1367 · Cited by 953 · see citing works
Plzf is required in adult male germ cells for stem cell self-renewal
Buaas, F. W., Kirsh, A. L., Sharma, M., McLean, D. J., Morris, J. L., Griswold, M. D., de Rooij, D. G., & Braun, R. E. (2004) · Nature Genetics · doi:10.1038/ng1366 · Cited by 882 · see citing works
Carcinoma‐in‐situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma
Skakkebæk, N. E., Berthelsen, J., Giwercman, A., & Müller, J. (1987) · International Journal of Andrology · doi:10.1111/j.1365-2605.1987.tb00161.x · Cited by 741 · see citing works
The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences.
Löwer, R., Löwer, J., & Kurth, R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.11.5177 · Cited by 691 · see citing works
Repeats in genomic DNA: mining and meaning.
Jurka, J. (1998) · Current Opinion in Structural Biology · doi:10.1016/s0959-440x(98)80067-5 · Cited by 301 · see citing works
Plzf regulates limb and axial skeletal patterning
Barna, M., Hawe, N., Niswander, L. A., & Pandolfi, P. P. (2000) · Nature Genetics · doi:10.1038/76014 · Cited by 279 · see citing works
Identification of human endogenous retroviruses with complex mRNA expression and particle formation.
Löwer, R., Boller, K., Hasenmaier, B., Korbmacher, C., Müller-Lantzsch, N., Löwer, J., & Kurth, R. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.10.4480 · Cited by 268 · see citing works
Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans
Barbulescu, M., Turner, G., Seaman, M. I., Deinard, A. S., Kidd, K. K., & Lenz, J. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80390-x · Cited by 244 · see citing works
Identification of a Rev-related protein by analysis of spliced transcripts of the human endogenous retroviruses HTDV/HERV-K
Löwer, R., Tönjes, R. R., Korbmacher, C., Kurth, R., & Löwer, J. (1995) · Journal of Virology · doi:10.1128/jvi.69.1.141-149.1995 · Cited by 201 · see citing works
Pathology of Germ Cell Tumors of Testis
Mostofi, F. K. (1980) · Cancer · doi:10.1002/cncr.1980.45.s7.1735 · Cited by 191 · see citing works
Pathogenesis of testicular germ cell tumours
Looijenga, L. H. J. (1999) · Reviews of Reproduction · doi:10.1530/ror.0.0040090 · Cited by 188 · see citing works
Clues to the Aetiology of Testicular Germ Cell Tumours from Descriptive Epidemiology
Møller, H. (1993) · European Urology · doi:10.1159/000474564 · Cited by 184 · see citing works
cORF and RcRE, the Rev/Rex and RRE/RxRE Homologues of the Human Endogenous Retrovirus Family HTDV/HERV-K
Magin, C., Löwer, R., & Löwer, J. (1999) · Journal of Virology · doi:10.1128/jvi.73.11.9496-9507.1999 · Cited by 150 · see citing works
An ancient family of human endogenous retroviruses encodes a functional homolog of the HIV-1 Rev protein.
Yang, J., Bogerd, H., Peng, S., Wiegand, H. L., Truant, R., & Cullen, B. (1999) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.96.23.13404 · Cited by 147 · see citing works
An almost-intact human endogenous retrovirus K on human chromosome 7
Mayer, J. M., Sauter, M., Rácz, A., Scherer, D., Mueller‐Lantzsch, N., & Meese, E. U. (1999) · Nature Genetics · doi:10.1038/6766 · Cited by 143 · see citing works
Self-citation
Tumor cells expressing a retroviral envelope escape immune rejection in vivo
Mangeney, M., & Heidmann, T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14920 · Cited by 137 · see citing works
Our retroviral heritage
Patience, C. (1997) · Trends in Genetics · doi:10.1016/s0168-9525(97)01057-3 · Cited by 136 · see citing works
Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein
Boese, A. S., Sauter, M., Galli, U., Best, B. A., Herbst, H., Mayer, J. M., Kremmer, E., Roemer, K., & Müeller, A. (2000) · Oncogene · doi:10.1038/sj.onc.1203794 · Cited by 125 · see citing works
Self-citation
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McConnell, M. J., Chevallier, N., Berkofsky‐Fessler, W., Giltnane, J. M., Malani, R. B., Staudt, L. M., & Licht, J. D. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9375-9388.2003 · Cited by 120 · see citing works
Evolution and biological significance of human retroelements
Leib‐Mösch, C., & Seifarth, W. (1995) · Virus Genes · doi:10.1007/bf01728654 · Cited by 71 · see citing works
Interstitial cell tumour and germ cell tumour with carcinoma in situ in rabbit testes
Veeramachaneni, & Vandewoude (1999) · International Journal of Andrology · doi:10.1046/j.1365-2605.1999.00154.x · Cited by 44 · see citing works

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“In 2005, Galli and Co-workers demonstrated that transgenic mice expressing Rec show disturbances in germ cell development and that some animals develop lesions similar to the predecessor lesions of classical seminomas in humans (138).”
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“3), when expressed as a transgene inmice, interferes with germ cell development and causes lesions that resemble carcinoma [64].”
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Chan, S. M., Sapir, T., Park, S. S., Rual, J.-F. M., Contreras-Galindo, R., Reiner, O., & Markovitz, D. M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0212970 · Cited by 45 · see citing works
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Díaz-Carballo, D., Klein, J., Acikelli, A. H., Wilk, C., Saka, S., Jastrow, H., Wennemuth, G., Dammann, P., Giger-Pabst, U., Khosrawipour, V., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.21606 · Cited by 43 · see citing works
The role of human endogenous retroviruses in melanoma
Singh, S., Kaye, S., Gore, M. E., McClure, M. O., & Bunker, C. B. (2009) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2009.09415.x · Cited by 41 · see citing works
Human endogenous retrovirus HERV-K(HML-2) encodes a stable signal peptide with biological properties distinct from Rec
Ruggieri, A., Maldener, E., Sauter, M., Mueller‐Lantzsch, N., Meese, E. U., Fackler, O., & Mayer, J. M. (2009) · Retrovirology · doi:10.1186/1742-4690-6-17 · Cited by 40 · see citing works
Self-citation
Endogenous retroviruses and human disease
Dolei, A. (2006) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2.1.149 · Cited by 40 · see citing works
The NP9 protein encoded by the human endogenous retrovirus HERV‐K(HML‐2) negatively regulates gene activation of the Epstein‐Barr virus nuclear antigen 2 (EBNA2)
Groß, H., Barth, S., Pfuhl, T., Willnecker, V., Spurk, A., Gurtsevitch, V., Sauter, M., Hu, B., Noeßner, E., Mueller‐Lantzsch, N., et al. (2010) · International Journal of Cancer · doi:10.1002/ijc.25760 · Cited by 35 · see citing works
Self-citation
Staufen-1 Interacts with the Human Endogenous Retrovirus Family HERV-K(HML-2) Rec and Gag Proteins and Increases Virion Production
Hanke, K., Höhn, O., Liedgens, L., Fiddeke, K., Wamara, J., Kurth, R., & Bannert, N. (2013) · Journal of Virology · doi:10.1128/jvi.03031-12 · Cited by 34 · see citing works
Meiosis and retrotransposon silencing during germ cell development in mice
Öllinger, R., Reichmann, J., & Adams, I. R. (2010) · Differentiation · doi:10.1016/j.diff.2009.10.004 · Cited by 33 · see citing works
Human Endogenous Retrovirus K Rec Forms a Regulatory Loop with MITF that Opposes the Progression of Melanoma to an Invasive Stage
Singh, M., Cai, H., Bunse, M., Feschotte, C., & Izsvák, Z. (2020) · Viruses · doi:10.3390/v12111303 · Cited by 31 · see citing works
Human-Specific Endogenous Retroviruses
Buzdin, A. A. (2007) · The Scientific World JOURNAL · doi:10.1100/tsw.2007.270 · Cited by 30 · see citing works
Application of stem cell markers in search for neoplastic germ cells in dysgenetic gonads, extragonadal tumours, and in semen of infertile men
Hoei‐Hansen, C. E. (2008) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2007.12.007 · Cited by 29 · see citing works
An Ecological Framework of the Human Virome Provides Classification of Current Knowledge and Identifies Areas of Forthcoming Discovery.
Parker, M. T. (2016) · PubMed Central · Cited by 25 · see citing works
Development of real-time PCRs for detection and quantitation of human MMTV-like (HML) sequences
Muradrasoli, S., Quigley, A. F., Hu, L., Blikstad, V., & Blomberg, J. (2006) · Journal of Virological Methods · doi:10.1016/j.jviromet.2006.04.005 · Cited by 24 · see citing works
Expression pattern analysis of transcribed HERV sequences is complicated by ex vivorecombination
Flockerzi, A., Maydt, J., Frank, O., Ruggieri, A., Maldener, E., Seifarth, W., Medstrand, P., Lengauer, T., Meyerhans, A., Leib‐Mösch, C., et al. (2007) · Retrovirology · doi:10.1186/1742-4690-4-39 · Cited by 23 · see citing works
Overexpression of TET dioxygenases in seminomas associates with low levels of DNA methylation and hydroxymethylation
Benešová, M., Trejbalová, K., Kučerová, D., Vernerová, Z., Hron, T., Szabó, Á., Amouroux, R., Klézl, P., Hájková, P., & Hejnar, J. (2017) · Molecular Carcinogenesis · doi:10.1002/mc.22638 · Cited by 22 · see citing works
Expression-analysis of the human endogenous retrovirus HERV-K in human astrocytic tumors
Kessler, A. F., Wiesner, M., Denner, J., Kämmerer, U., Vince, G. H., Linsenmann, T., Löhr, M., Ernestus, R., & Hagemann, C. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-159 · Cited by 21 · see citing works
Exploring HERV-K (HML-2) Influence in Cancer and Prospects for Therapeutic Interventions
Costa, B., & Vale, N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914631 · Cited by 19 · see citing works
Differentiation-Dependent Regulation of Human Endogenous Retrovirus K Sequences and Neighboring Genes in Germ Cell Tumor Cells
Mueller, T., Hantsch, C., Volkmer, I., & Staege, M. S. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01253 · Cited by 19 · see citing works
Retroviruses of the Human Virobiota: The Recycling of Viral Genes and the Resulting Advantages for Human Hosts During Evolution
Luganini, A., & Gribaudo, G. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01140 · Cited by 17 · see citing works
Human Endogenous Retroviruses as Biomedicine Markers
Song, Y., Li, X., Wei, X., & Cui, J. (2021) · Virologica Sinica · doi:10.1007/s12250-021-00387-7 · Cited by 17 · see citing works
An alternative approach to medical genetics based on modern evolutionary biology. Part 4: HERVs in cancer
Ryan, F. (2009) · Journal of the Royal Society of Medicine · doi:10.1258/jrsm.2009.090289 · Cited by 17 · see citing works
Human endogenous retrovirus regulates the initiation and progression of cancers (Review)
Sahu, S., Singh, B., & Rai, A. (2022) · Molecular and Clinical Oncology · doi:10.3892/mco.2022.2576 · Cited by 16 · see citing works
Mammalian Endogenous Retroviruses
Mager, D. L., & Stoye, J. P. (2015) · ASM Press eBooks · doi:10.1128/9781555819217.ch47 · Cited by 16 · see citing works
A Human Endogenous Bornavirus-Like Nucleoprotein Encodes a Mitochondrial Protein Associated with Cell Viability
Fujino, K., Horie, M., Kojima, S., Shimizu, S., Nabekura, A., Kobayashi, H., Makino, A., Honda, T., & Tomonaga, K. (2021) · Journal of Virology · doi:10.1128/jvi.02030-20 · Cited by 15 · see citing works
Expression Profiles of Endogenous Retroviruses in Old World Monkeys
Stengel, A., Roos, C., Hunsmann, G., Seifarth, W., Leib‐Mösch, C., & Greenwood, A. D. (2006) · Journal of Virology · doi:10.1128/jvi.80.9.4415-4421.2006 · Cited by 13 · see citing works
A human endogenous retrovirus encoded protease potentially cleaves numerous cellular proteins
Rigogliuso, G., Biniossek, M. L., Goodier, J. L., Mayer, B. A., Pereira, G., Schilling, O., Meese, E. U., & Mayer, J. M. (2019) · Mobile DNA · doi:10.1186/s13100-019-0178-z · Cited by 12 · see citing works
Investigation of somatic single nucleotide variations in human endogenous retrovirus elements and their potential association with cancer
Chang, T.-C., Goud, S., Torcivia-Rodriguez, J., Hu, Y., Pan, Q., Kahsay, R., Blomberg, J., & Mazumder, R. (2019) · PLoS ONE · doi:10.1371/journal.pone.0213770 · Cited by 11 · see citing works
Isolation and Characterization of a Novel Noncoding RNA from Nickel-Induced Lung Cancer
Zhang, J., Zhou, Y., Wu, Y., Ma, L., Fan, Y., Kang, X., Shi, H., & Zhang, J. (2012) · Biological Trace Element Research · doi:10.1007/s12011-012-9460-3 · Cited by 10 · see citing works
Expression of human endogenous retrovirus-K coincides with that of micro-RNA-663 and -638 in germ-cell tumor cells.
Kraus, B., Mönk, B., Sliva, K., & Schnierle, B. S. (2012) · PubMed · Cited by 9 · see citing works
Biochemical Analysis of the Complex between the Tetrameric Export Adapter Protein Rec of HERV-K/HML-2 and the Responsive RNA Element RcRE pck30
Langner, J. S., Fuchs, N. V., Hoffmann, J., Wittmann, A., Brutschy, B., Löwer, R., & Suess, B. (2012) · Journal of Virology · doi:10.1128/jvi.00121-12 · Cited by 9 · see citing works
Transposable elements in human cancers by genome-wide EST alignment
Kim, D., Huh, J., & Kim, H. (2007) · Genes & Genetic Systems · doi:10.1266/ggs.82.145 · Cited by 8 · see citing works
A functional analysis of retroviral endogenous inserts in view of human genome evolution
Buzdin, A. A. (2010) · Russian Journal of Bioorganic Chemistry · doi:10.1134/s1068162010010048 · Cited by 7 · see citing works
Involvement of Endogenous Retroviruses in Prion Diseases
Lee, Y.-J., Jeong, B., Choi, E., & Kim, Y. (2013) · Pathogens · doi:10.3390/pathogens2030533 · Cited by 6 · see citing works
Noncoding RNAs in Human Diseases
Szymański, M., & Barciszewski, J. (2008) · Springer eBooks · doi:10.1007/978-3-540-78709-9_12 · Cited by 6 · see citing works
Characterization of HERV-K (HML-2) Rec proteins encoded in the human genome and their post-transcriptional function
Zurowska, K., Dzhivhuho, G. A., Grabski, D. F., Rekosh, D. M., & Hammarskjöld, M. (2025) · Journal of Virology · doi:10.1128/jvi.01515-25 · Cited by 4 · see citing works
The Role of Transposable Elements in Emergence of Metazoa
Mustafin, R. N., & Хуснутдинова, Э. К. (2018) · Biochemistry (Moscow) · doi:10.1134/s000629791803001x · Cited by 4 · see citing works
Human Endogenous Retrovirus K (HERV-K) can drive gene expression as a promoter in Caenorhabditis elegans
Durnaoglu, S., Kim, H., Ahnn, J., & Lee, S.-K. (2020) · BMB Reports · doi:10.5483/bmbrep.2020.53.10.150 · Cited by 4 · see citing works
Sheep stromal‐epithelial cell interactions and ovarian tumor progression
Wang‐Johanning, F., Huang, M. L., Liu, J., Rycaj, K., Plummer, J. B., Barnhart, K. F., Satterfield, W. C., & Johanning, G. L. (2007) · International Journal of Cancer · doi:10.1002/ijc.22960 · Cited by 4 · see citing works
A plan or pandemonium? The conundrum of retrotransposon activation in cancer
Zueva, E. (2025) · Mobile DNA · doi:10.1186/s13100-025-00368-7 · Cited by 3 · see citing works
Activation of human endogenous retroviruses by Sox proteins induces cell apoptosis via the caspase-3 pathway
Hossain, M. J., Monde, N., Sasaki, H., Nyame, P., Amesimeku, W. A. O., Terasawa, H., Matsumura, S., Matsui, T., Tsutsuki, H., Maeda, Y., et al. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1604022 · Cited by 2 · see citing works
Downregulation of inhibitor of apoptosis protein induces apoptosis and suppresses stemness maintenance in testicular teratoma
Li, G., Liao, M., Li, S., You, J., Wang, J., Wei, L., Yang, C., Xu, H., Xiao, H., & Chen, H. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10835 · Cited by 1 · see citing works
Genome‐wide identification of endogenous retrovirus elements and their active transcription in mink genome
Li, Z., Wang, Q., Lv, N., Xu, G., Yang, X., & Zhu, B. (2023) · mLife · doi:10.1002/mlf2.12074 · Cited by 1 · see citing works
Targeting endogenous retrovirus gene transcription in human cancersPreprint
Lin, A. T., Santander, C. G., Marchi, E., Karamitros, T., Katzourakis, A., & Magiorkinis, G. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/449686 · Cited by 1 · see citing works
HERV-K HML-2 transcription in diverse cancers is related with cancer stem cell and epithelial-mesenchymal transition markersPreprint
Lin, A. T., Santander, C. G., do Nascimento, F. F., Marchi, E., Karamitros, T., Katzourakis, A., & Magiorkinis, G. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/451997 · Cited by 1 · see citing works

Expression of human endogenous retrovirus K elements in germ cell and trophoblastic tumors.
Herbst, H., Sauter, M., & Müeller, A. (1996) · Europe PMC (PubMed Central) · Cited by 109 · see citing works
Self-citation
Human endogenous retrovirus (HERV)‐K transcripts in germ cell and trophoblastic tumours
Herbst, H., Sauter, M., Kühler-Obbarius, C., Löning, T., & MUELLER‐LANTZSCH, N. (1998) · Apmis · doi:10.1111/j.1699-0463.1998.tb01338.x · Cited by 49 · see citing works
Self-citation
Germ Cell Expression of an Isolated Human Endogenous Retroviral Long Terminal Repeat of the HERV-K/HTDV Family in Transgenic Mice
Casau, A. E., Vaughan, J. E., Lozano, G., & Levine, A. J. (1999) · Journal of Virology · doi:10.1128/jvi.73.12.9976-9983.1999 · Cited by 26 · see citing works
Expression of Human Endogenous Retroviruses HERV-K/HTDV in Germ Cell Tumours: Possible Biological Role and Clinical Application
Kleiman, A., Senyuta, N. B., Trjakin, A., Vinogradova, T., Karseladze, A. I., Gurtsrvitch, V., & Tjulandin, S. (2002) · Springer eBooks · doi:10.1007/978-1-4471-3281-3_7
Human endogenous retrovirus (HERV)-K transcripts in gonadoblastomas and gonadoblastoma-derived germ cell tumours
Herbst, H., Kühler-Obbarius, C., Lauke, H., Sauter, M., Müeller, A., Harms, D., & Löning, T. (1999) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s004280050298 · Cited by 36 · see citing works
Self-citation

Authors: Galli, U. M., Sauter, M., Lecher, B., Maurer, S., Herbst, H., Roemer, K., & Mueller-Lantzsch, N.
Affiliations: Saarland University (DE)
Johannes Gutenberg University Mainz (DE)
University of Münster (DE)
ORCID: Herbst, Hermann
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2005-02-28
Volume: 24
Issue: 19
Pages: 3223-3228
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1208543
OpenAlex: W2075780070
Cited by: 120
References: 22
Citations by year: 2025: 6 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 7 · 2020: 5 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 7 · 2015: 5 · 2014: 6 · 2013: 11 · 2012: 8
FWCI: 7.58
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Health Sciences › Medicine › Surgery › Testicular diseases and treatments
Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords: HERV-K, germ cell tumors, germ cell development, carcinoma in situ, seminoma, transgenic mouse model, rev gene, retroviral gene expression
MeSH terms: Animals, Carcinoma in Situ, Germ Cells, Humans, Male, Mice, Transgenic, Microscopy, Fluorescence, Models, Genetic, Neoplasms, Germ Cell and Embryonal, RNA, Messenger, Seminiferous Tubules, Time Factors, Viral Envelope Proteins, Blotting, Western, Apoptosis, Alternative Splicing, Protein Structure, Tertiary, Germinoma, Endogenous Retroviruses, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, Mice

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

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