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Published on: August 25, 2017
Expression of human endogenous retrovirus K in melanomas and melanoma cell lines
Kristina Büscher1, Uwe Trefzer, Maja Hofmann
1Robert Koch-Institute and Department of Dermatology, Campus Charité-Mitte, Charité-University Medicine Berlin, Berlin, Germany.
Abstract:
The human endogenous retrovirus K family (HERV-K) comprises 30 to 50 closely related proviruses, most of which are defective. In contrast to all other human endogenous retroviruses, some HERV-K proviruses have maintained open reading frames for all viral proteins. In addition to the structural proteins Gag and Env and the reverse transcriptase, two regulatory proteins (Rec and Np9) have been described. Malignant melanoma has the highest mortality among skin cancers and is particularly aggressive. To study the expression of HERV-K, a set of seven primers was developed that allows discrimination between full-length and spliced mRNA and mRNA from deleted and undeleted proviruses. Expression of full-length mRNA from deleted and undeleted proviruses was detected in all human cells investigated. Expression of spliced env and rec was detected in a teratocarcinoma cell line, in 45% of the metastatic melanoma biopsies, and in 44% of the melanoma cell lines. In normal neonatal melanocytes, spliced rec was detected but not spliced env. Viral proteins were shown to be expressed in primary melanomas, metastases, and melanoma cell lines by immunohistochemistry, immunofluorescence, and Western blot analyses using specific antisera. For the first time, antibodies against HERV-K were found in melanoma patients. Melanomas are, in addition to teratocarcinomas and human breast cancer, the third tumor type with enhanced expression of HERV-K.
Insights
Human endogenous retrovirus K (HERV-K) is expressed in melanoma, with viral proteins detected in tumors and antibodies found in patients. This suggests HERV-K involvement in melanoma development.
Area of Science:
- Retroviruses
- Oncology
- Molecular Biology
Background:
- Human endogenous retrovirus K (HERV-K) is a family of retroviruses, with some maintaining complete coding potential.
- Malignant melanoma is an aggressive skin cancer with high mortality.
- HERV-K expression is implicated in various cancers, including breast cancer and teratocarcinomas.
Purpose of the Study:
- To investigate the expression of HERV-K in malignant melanoma.
- To determine if HERV-K proteins and patient antibodies are present in melanoma tissues and cell lines.
Main Methods:
- Developed specific primers to differentiate HERV-K mRNA variants (full-length, spliced, deleted, undeleted).
- Detected mRNA expression using RT-PCR.
- Confirmed protein expression and presence of antibodies via immunohistochemistry, immunofluorescence, and Western blot analyses.
Main Results:
- Full-length HERV-K mRNA was detected in all human cells studied.
- Spliced HERV-K env and rec mRNA were found in teratocarcinoma cell lines, 45% of metastatic melanoma biopsies, and 44% of melanoma cell lines.
- HERV-K viral proteins were expressed in primary melanomas, metastases, and melanoma cell lines.
- For the first time, antibodies against HERV-K were detected in melanoma patients.
Conclusions:
- Melanoma exhibits enhanced HERV-K expression, similar to teratocarcinomas and breast cancer.
- HERV-K is the third tumor type, alongside teratocarcinomas and breast cancer, showing enhanced expression.
- The presence of HERV-K proteins and patient antibodies suggests a potential role in melanoma pathogenesis.
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