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 a poptosis sensitivity were selected for in nonmetastatic and metastatic variants of the LNCaP human prostate carcinoma line that had been iso lated from tumors grown orthotopically in the prostate glands and regi onal Lymph nodes of nude mice, The nonmetastatic LNCaP-Pro5 cells were significantly more sensitive to thapsigargin-induced apoptosis than w ere the metastatic LNCaP-LN3 cells, as measured by viability, DNA frag mentation, and interleukin 1 beta-converting enzyme family-mediated cl eavage of the DNA repair enzyme, poly(ADP-ribose) polymerase. Apoptosi s resistance in the metastatic cells was associated ffith higher level s of expression of the cell death suppressor BCL-2 and lower levels of the death promoters BAX and BAli than were detected in the nonmetasta tic LNCaP-Pro5 cells, whereas levels of two other BCL-2 family members (BCL-X(L) and BAD) were indistinguishable, Our data support the hypot hesis that apoptosis resistance contributes to prostate cancer metasta sis and that elevated expression of BCL-2 is involved.