Correlation between complementation group for immortality and the cellular distribution of mortalin.

The dominance of cellular senescence over the immortal phenotype has been demonstrated by cell fusion experiments utilizing human and mouse cells. Mortalin, a novel 66-kDa member of the murine hsp70 family of proteins, has recently been identified as a marker of the mortal phenotype by virtue of its characteristic cytosolic distribution in mortal cells. Here we report the mortalin immunostaining observations on 21 human cell lines. These cell lines have previously been assigned by somatic cell hybridization analysis to one (18 lines) or more than one (3 lines) of the four complementation groups (A, B, C, and D) for immortalization. Four patterns of mortalin immunostaining were observed: granular-juxtanuclear cap, granular-gradient from nuclear to cell membrane, granular-juxtanuclear arch, and fibrous-perinuclear. In 17 of 18 cell lines assigned to a single complementation group, the mortalin staining corresponded with the complementation group. In two of the three cell lines previously assigned to multiple complementation groups, the mortalin staining corresponded to one of the assigned groups. Two cell lines, however, exhibited staining patterns which did not match to their assigned complementation groups. The basis of correlation between cellular distribution of mortalin and the complementation group remains unclear at present. However, the data (i) suggest that the intracellular distribution of mortalin can be used to distinguish mortal and immortal cells, confirming the association of mortalin with senescence; (ii) provide supportive evidence for the existence of at least four different pathways of immortalization in human cells; and (iii) indicate that mortalin is involved in processes that result in immortalization.