Expression of human endogenous retrovirus K envelope transcripts in human breast cancer

Purpose: We investigated the expression of human endogenous retroviral (HER V) sequences in breast cancer. Experimental Design: Reverse transcription-PCR (RT-PCR) was used to examine expression of the envelope (env) region of ERV3, HERV-E4-1, and HERV-K in breast cancer cell lines, human breast tumor samples, adjacent uninvolved b reast tissues, nonmalignant breast tissues, and placenta. Expression of HER V transcripts was confirmed by Northern blot analysis and in situ hybridiza tion (ISH). To evaluate coding potential, amplified HERV sequences were clo ned into vectors for expression and sequence analysis. Results: No expression of ERV3 or HERV-E4-1 RNA was detected in the analyze d breast samples. In contrast, HERV-K transcripts were detected in most bre ast cancer cell lines and many breast tumor tissues. Expression was detecte d in a small percentage of matched, uninvolved breast tissues and in placen tas but not nonmalignant breast tissues. In HERV-K-positive breast cancer t issues, Northern blot analysis demonstrated full-length proviral and splice d env transcripts. ISH demonstrated expression of HERV-K transcripts in bre ast tumor cells but not in normal or uninvolved breast epithelial cells. In dependently isolated clones of HERV-K env cDNA generated recombinant protei ns of the expected size. Sequence analysis of env cDNA clones derived from four breast tumor samples revealed > 97% identity with the type I HERV-K102 , with no premature termination codons, Independent isolates from the same breast tumor sample showed nucleotide sequence differences, suggesting that multiple loci may be transcribed. Conclusions: These data indicate that HERV-K transcripts with coding potent ial for the envelope region are expressed frequently in human breast cancer .