Apoptosis resistance increases with metastatic potential in cells of the human LNCaP prostate carcinoma line.
The aim of this study was to determine whether stable differences in apoptosis sensitivity were selected for in nonmetastatic and metastatic variants of the LNCaP human prostate carcinoma line that had been isolated from tumors grown orthotopically in the prostate glands and regional lymph nodes of nude mice. The nonmetastatic LNCaP-Pro5 cells were significantly more sensitive to thapsigargin-induced apoptosis than were the metastatic LNCaP-LN3 cells, as measured by viability, DNA fragmentation, and interleukin 1beta-converting enzyme family-mediated cleavage of the DNA repair enzyme, poly(ADP-ribose) polymerase. Apoptosis resistance in the metastatic cells was associated with higher levels of expression of the cell death suppressor BCL-2 and lower levels of the death promoters BAX and BAK than were detected in the nonmetastatic LNCaP-Pro5 cells, whereas levels of two other BCL-2 family members (BCL-X(L) and BAD) were indistinguishable. Our data support the hypothesis that apoptosis resistance contributes to prostate cancer metastasis and that elevated expression of BCL-2 is involved.
McConkey
D J
DJ
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. David_McConkey@isqm.mda.uth.tmc.edu
Greene
G
G
Pettaway
C A
CA
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002273:Carcinogens / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; D009363:Neoplasm Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019284:Thapsigargin; D004317:Doxorubicin; C499320:PARP1 protein, human; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases