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

• Published in: Apoptosis (London) 1999-12, Vol.4 (6), p.429-440
• Main Authors: Kay, S, Michowitz, M, Donin, N, Katzenelson, D, Siegal, A, Sinai, J, Ravia, J, Pinchassov, A, Leibovici, J
• Format: Article
• Language: English
• Subjects: Apoptosis; Cells; Cellular biology; Lymphoma; Tumors
• ISSN: 1360-8185; 1573-675X
• DOI: 10.1023/A:1009648325350

Resistance to apoptosis may be related to tumor progression, due to the implications it might have on both tumor mass and genetic instability. We compared the tendency to spontaneous apoptosis and the proliferative capacity of 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 potential). We further compared the expression of several apoptosis-related genes. Cell proliferative capacity did not appear to determine malignant behavior since, on the whole, a decrease in S + G2M fraction was observed with increasing malignancy. Sensitivity to apoptotic cell death decreased with increasing malignancy when comparing the TAU-45, TAU-47, TAU-44 and TAU-33 variants, suggesting a role of reduced apoptosis in this T-cell lymphoma. An increase in Bcl-2 content with increasing aggressiveness among these variants, implicates this protein in this tumor progression-related resistance to apoptosis. However, the two variants of highest malignancy, TAU-42 and TAU-46, did not follow the same trend, since they displayed a relatively high content in apoptotic cells and a low Bcl-2 content. Fas receptor expression did not correlate with tendency to apoptosis, indicating that malignant behavior in the AKR lymphoma does not depend on CD95/Fas/APO1 downregulation. Overexpression of p53 was observed only in one of the variants of lowest malignancy.