Human endogenous retrovirus (HERV)‐K transcripts in germ cell and trophoblastic tumours

Abstract

Prompted by the observation of retroviral particle formation in teratocarcinoma cell lines and the consistent finding of antibodies against Gag and Env proteins encoded by human endogenous retrovirus (HERV)‐K genomes in the sera of patients with classical seminoma, we studied ovarian and testicular germ cell tumours, their precursor lesions, dysgenetic gonads, and trophoblast lesions for expression of HERV‐K sequences by in situ hybridization using radioactive and non‐radioactive probes. HERV‐K transcripts were detected in all testicular and ovarian germ cell tumours with the exception of teratomas and spermatocytic seminomas. HERV‐K expression was also common to testicular carcinoma in situ as well as gonocytes of dysgenetic gonads. Among gestational trophoblastic lesions, HERV‐K expression was regularly found in choriocarcinomas, but not in molar lesions. The patterns of HERV‐K expression suggest a common molecular pathogenesis of most germ cell tumour entities and malignant gestational trophoblastic disease. They furthermore support the concept of carcinoma in situ as a precursor lesion common to most testicular germ cell neoplasms. The detection of HERV‐K gene products in body fluids and tissues may aid diagnosis and monitoring of germ cell tumours and related lesions.

Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein

“…Furthermore, cyclin A has recently been identi®ed as one PLZF target gene, and cyclin A subtypes are considered to possess regulatory functions in murine spermatogenesis (Ravnik and Wolgemuth, 1999). Malignant germ cell tumors in humans exhibit di erent states of di erentiation; they all, however, arise from the common (CIS/TIN) precursor lesion (Skakkebaek, 1972), which already displays HERV-K(HML-2) expression (Herbst et al, 1998). CIS cells resemble undi erentiated gonocytes that normally di erentiate into spermatogonia in late fetal development (Skakkebaek et al, 1987), and any delay in gonocyte maturation seems to be associated with an increased risk of testicular germ-cell cancer (Heimdal et al, 1997).…”

“…The same cORF sequence was inserted into the run-o transcription vector pGEM1 for generation of in situ hybridization RNA probes. The gag and env probes were as previously described (Herbst et al, 1996). Plasmid pCEP4-cORF was constructed by inserting full-length cORF into the BamHI-site of pCEP4 (Invitrogen).…”

“…In situ hybridization was carried out as previously described (Herbst et al, 1996). cORF protein was detected with the above speci®ed polyclonal and monoclonal antibodies on para n sections from nude mice tumors and human GCT samples by the APAAP technique, using mouse anti-rabbit Ig antibodies, mouse anti-alkaline phosphatase antibodies and rat anti-alkaline phosphatase antibodies.…”

DNA methylation in cancer: too much, but also too little

“…The transcripts included HERV-K env RNA capable of encoding the HERV-K envelope protein. Moreover, high-level expression of HERV-K gag and env RNA is associated with germ cell and trophoblastic tumors (Herbst et al, 1996). That env RNA was detected in most assayed term placental samples (Wang-Johanning et al, 2001) may be related to much of term placental tissue being of trophoblast origin and placental DNA displaying global genomic hypomethylation (Ehrlich et al, 1982).…”

Evidence for a protein related immunologically to the jaagsiekte sheep retrovirus in some human lung tumours

“…An exogenous type B/D retrovirus (jaagsiekte sheep retrovirus (JSRV)) is the causal agent of SPA [7] and appears to replicate mainly in the transformed epithelial cells [8]. Renewed speculation regarding the involvement of a retrovirus in BAC [9] has been supported by the association of retroviruses, other than human immunodeficiency virus and human T-cell leukaemia virus, with several diseases of humans, such as seminoma [10], undifferentiated germ cell tumours [11], multiple sclerosis [12], acute-onset type I diabetes [13] and Sjo Ègren's syndrome [14]. In order to address this issue, a panel of human lung tumours and relevant nontumour lung lesions were examined immunohistochemically using an antiserum to JSRV capsid protein (JSRV-CA).…”