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A Novel Gene from the Human Endogenous Retrovirus K Expressed in Transformed Cells¹

Institut für Mikrobiologie und Hygiene, Abteilung Virologie, Geb. 47 [V. A., M. S., E. K., B. B., N. M-L.], and Institut für Humangenetik, Geb. 60 [E. M.], Universitätskliniken des Saarlandes, Homburg/Saar D-66421, Germany; and Blokhin Cancer Research Center, Russian Academy for Medical Science, Moscow 115478, Russia [A. K.]

Purpose: We investigated the expression of human endogenous retrovirus K (HERV-K) transcripts in various tumor tissues and transformed cell lines.

Experimental Design: We performed reverse transcription-PCR analysis to examine expression of env reading frame transcripts in mammary carcinoma biopsies, germ-cell tumor samples, ovarian carcinomas, and lymphocytes of leukemic patients, as well as in a variety of transformed cell lines. The novel np9 gene was analyzed by sequencing. Expression of the recombinant Np9 protein was shown by Western blot analysis and immunofluorescence studies with polyclonal Np9-specific antibodies. Subcellular localization was determined with a Np9-enhanced-green fluorescence protein fusion protein, and the effects of Np9 on cell proliferation and survival were studied in growth and standard colony formation assays.

Results: We have identified a novel gene, np9, within the HERV-K env-reading frame that gives rise to a 9-kDa protein localized predominantly in the cell nucleus. np9 transcript results from a novel, HERV-K type 1-specific splice donor site and is expressed in various tumor tissues and transformed cell lines but not in normal, nontransformed cells.

Conclusion: The highly specific expression of np9 in tumor tissue suggests that the protein may possess a function in tumorigenesis.

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