A gene on 6q 14-21 restores senescence to immortal ovarian tumor cells.

We have identified a gene on 6q14-21 which restores senescence to immortal ovarian tumor cells. Single gpt tagged human chromosomes, present in mouse/human monochromosomal hybrids, were introduced into immortal human and rat ovarian tumor cells via microcell fusion. Analysis of chromosome transfer clones for cell morphology and growth properties revealed that chromosome 6 or 6q restored senescence to both human and rat ovarian tumor cells while chromosomes 10 or 14 did not affect the proliferative potential of these cells. Reversion to immortal growth concordant with loss of the donor chromosome confirmed the presence of a senescence gene on 6q. During continuous maintenance of microcell hybrids in MX medium, rare immortal revertant clones grew out of the human and rat senescent cell populations. Analysis of independent revertant clones of rat cells, for chromosome 6 markers, revealed a common deletion of chromosomal region 6q14-21 in all revertants. Restoration of senescence following introduction of a gpt tagged chromosome segment 6q13-21 into human and rat ovarian tumor cells confirmed the location of a senescence gene in this region. In contrast, introduction of a chromosome 6 lacking the region 6q14-21 did not impart senescence in these cells. Based on these results we assigned the senescence gene (SEN 6A) to region 6q14-21.