RESUMO
To elucidate the role of some viral and cellular proteins in the occurrence and development of HERV-K-associated germ-cell tumors (GCT), reverse-transcription polymerase chain reaction using specific primers has been employed to study the transcription of the protein Rec HERV-K and the possible interaction of the protein Rec(cORF), that has transforming properties, and the cellular protein PLZF, that is a negative regulator of cell division, in human GCT tissues, in the testicular parenchyma adjacent to a tumor, and in the normal testicular tissues. It was shown that there was expression of Rec(cORF) of mRNA, rather than cellular PLZF in all malignant GCT tissues, this led to the conclusion that no interaction occured between the Rec HERV-K and PLZF proteins in the GCT cells. At the same time co-expression of Rec and PLZF protein was first revealed at the level of transcription in the testicular parenchyma adjacent to a tumor that exhibited carcinoma in situ cells. By taking into account that the protein Rec HERV-K has transforming activity and it is presumed to be Implicated in the development of GCT, the authors discuss a possible role in the Rec HERV-K/HTDV and cellular PLZF interaction in the pathogenesis of GST at the early stages of its genesis.
Assuntos
Transformação Celular Viral , Retrovirus Endógenos/metabolismo , Fatores de Transcrição Kruppel-Like/biossíntese , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/virologia , Proteínas do Envelope Viral/biossíntese , Transformação Celular Viral/genética , Retrovirus Endógenos/genética , Humanos , Fatores de Transcrição Kruppel-Like/genética , Masculino , Neoplasias Embrionárias de Células Germinativas/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica , RNA Viral/biossíntese , RNA Viral/genética , Testículo/metabolismo , Transcrição Gênica , Proteínas do Envelope Viral/genéticaRESUMO
Human germ cell tumors (GCT) have been found to be closely associated with the expression of HERV-K/HTDV proviruses and most patients with GCT produce antibodies to the major HERV-K/HTDV Gag and Env proteins. The findings have shown a strong association of the level of HERV-K/HTDV antibodies with the clinical course of the disease and therapy success, which makes it possible to confirm the fact that viral protein antibodies may be used as an additional marker of GCT.
Assuntos
Anticorpos Antivirais/sangue , Retrovirus Endógenos/imunologia , Neoplasias Embrionárias de Células Germinativas/sangue , Provírus/imunologia , Neoplasias Testiculares/sangue , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Linhagem Celular Tumoral , Progressão da Doença , Técnica Indireta de Fluorescência para Anticorpo , Produtos do Gene gag/imunologia , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/tratamento farmacológico , Proteínas do Envelope Viral/imunologiaRESUMO
Transcription of HERV-K/HTDV proviruses in various morphological forms of GCTs and in normal testicular parenchyma and placenta was studied by RT-PCR with specific primers discriminating type 1 proviruses from type 2 ones. The results indicate that transcription of type 2 HERV-K/HTDV proviruses takes place and mRNA of protein cORF, coded for only by type 2 proviruses, is synthesized in all malignant germinogenic tumors. In normal testicular tissue and placenta type 1 HERV-K/HTDV proviruses are expressed. No expression of HERV-K/HTDV proviruses was detected in nongerminogenic testicular tumors. Since cORF protein possesses transforming activity, its possible role in the pathogenesis of GCTs is discussed. Generation of humoral immune response to structural HERV-K/HTDV proteins in various morphological forms of GCTs confirmed the possibility of using antibodies to structural HERV-K/HTDV proteins as additional markers of GCTs.
