Differential expression of intracisternal A-particle transcripts in immunogenic versus tumorigenic S49 murine lymphoma cells

Tumorigenic S49 mouse lymphoma cells (T-25) were compared to their nontumor igenic (immunogenic) substrate-adherent descendants (T-25-Adh), using the d ifferential display technique. A 784-bp fragment with 92% sequence homology to the intracisternal A-particle (IAP) element family was isolated from th e latter cells. IAP sequences are endogenous, noninfectious retroviral elem ents that can undergo transpositions and act as mutagens. Expression of IAP transcripts (as detected by the isolated fragment) was 5- to 10-fold highe r in T-25-Adh cells than in T-25 cells. IAP RT-PCR cDNA clones derived from the immunogenic T-25-Adh cells, but not from T-25 cells, contain two disti nctive motifs: (i) a motif characteristic of IAP elements expressed in lymp hoid cells (lymphocyte specific, LS); (ii) a nonapeptide sequence known to stimulate cytotoxic T lymphocytes in a leukemia cell line expressing IAP se quences. In addition, expression of transcripts containing these motifs is enhanced in the immunogenic cells as opposed to the tumorigenic cells. Furt hermore, one of the IAP elements (belonging to the LSI subfamily) is specif ically hypomethylated in the DNA of the immunogenic cells. The above-mentio ned relationship was strengthened when tumorigenic revertants derived from T-25-Adh cells, as well as independently selected tumorigenic and immunogen ic S49 sublines, were studied. In all cases, enhanced immunogenicity was li nked to the up-regulation of specific IAP elements. No transpositions of LS 1 elements were observed among the different sublines studied. These findin gs suggest that, in the S49 lymphoma, selectively expressed IAP retroviral elements may function in a tumor suppressive capacity by affecting the immu nogenic potential of these cells. (C) 2000 Academic Press.