Release from apoptosis correlates with tumor progression in the AKR lymphoma.
Disturbance of apoptosis is an established factor in tumorigenesis. The role of apoptosis in tumor progression is not yet clear. In the present study we compared the tendency to spontaneous apoptosis (and the proliferative capacity) of tumor cells derived from primary (PT) and metastatic tumor (MT) cells of several AKR lymphoma variants. Apoptosis-related gene expression was also compared. Our results indicate that release from apoptosis has a role in the tumor progression of this T cell lymphoma. At the cellular level, a markedly lower apoptotic tendency was observed in MT than in PT cells. The existence of macrophages only in PT also supports the presence of apoptotic cells in local but not in MTs. By contrast, proliferative capacity does not determine tumor aggressiveness in this system. At the molecular level, we found a higher staining intensity for bcl-2 in MT than in PT cells, suggesting that bcl-2 might be responsible for the reduced apoptosis in MT compared to PT cells. Evidence for p53 overexpression was found in the MT cells of one of the variants but in none of the PT. Comparison of Fas receptor, unexpectedly showed an increased expression in MT versus PT cells, possibly indicating resistance to Fas-induced apoptosis in the MT cells.
Kay
S
S
Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, 69978, Tel-Aviv, Israel.
Donin
N
N
Michowitz
M
M
Katzenelson
D
D
Hiss
J
J
Schibi
G
G
Pinchassov
A
A
Leibovici
J
J
D000818:Animals; D017209:Apoptosis; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005434:Flow Cytometry; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008806:Mice, Inbred AKR; D008938:Mitosis; D009362:Neoplasm Metastasis / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
D004273:DNA, Neoplasm; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor