Apoptotic cell death and related gene expression in metastatic tumors of AKR lymphomas of varying malignancy

Resistance to apoptosis may be related to tumor progression, due to the imp lications it might have on both tumor mass and genetic instability. We comp ared the tendency to spontaneous apoptosis and the proliferative capacity o f metastatic growths of several AKR lymphoma variants (TAU-45, TAU-47, TAU- 44, TAU-33, TAU-42 and TAU-46, in the order of increasing metastatic potent ial). We further compared the expression of several apoptosis-related genes . Cell proliferative capacity did not appear to determine malignant behavio r since, on the whole, a decrease in S+G2M fraction was observed with incre asing malignancy. Sensitivity to apoptotic cell death decreased with increa sing malignancy when comparing the TAU-45, TAU-47, TAU-44 and TAU-33 varian ts, suggesting a role of reduced apoptosis in this T-cell lymphoma. An incr ease in Bcl-2 content with increasing aggressiveness among these variants, implicates this protein in this tumor progression-related resistance to apo ptosis. However, the two variants of highest malignancy, TAU-42 and TAU-46, did not follow the same trend, since they displayed a relatively high cont ent in apoptotic cells and a low Bcl-2 content. Fas receptor expression did not correlate with tendency to apoptosis, indicating that malignant behavi or in the AKR lymphoma does not depend on CD95/Fas/APO1 downregulation. Ove rexpression of p53 was observed only in one of the variants of lowest malig nancy.