Conditional expression of exogenous Bcl-X(S) triggers apoptosis in human melanoma cells in vitro and delays growth of melanoma xenografts.
The Bcl-2-related proteins Bcl-X(L) and Bcl-X(S) represent alternative splice products and exert opposite activities in the control of apoptosis, but their significance for melanoma is not yet clear. Applying the tetracycline-inducible expression system Tet-On, we found overexpression of Bcl-X(S) by itself sufficient to induce apoptosis in vitro in stably transfected human melanoma cell lines. Combination with proapoptotic agents such as etoposide, pamidronate, and ceramide resulted in additive proapoptotic effects, whereas Bcl-X(L) protected from apoptosis caused via CD95/Fas stimulation. In nude mice growth of melanoma xenotransplants derived from stably transfected cells was significantly reduced after induction of Bcl-X(S) by doxycycline. Our results indicate that Bcl-X proteins are of major importance for control of apoptosis in malignant melanoma.
Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Dermatology, Fabeckstrasse 60-62, 14195 Berlin, Germany.
Amir M
AM
Hossini
Jürgen
J
Eberle
Lothar F
LF
Fecker
Constantin E
CE
Orfanos
Christoph C
CC
Geilen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000648:ultrastructure; D002843:Chromatin / Q000648:ultrastructure; D002999:Clone Cells; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051020:bcl-X Protein; D019014:fas Receptor / Q000494:pharmacology
C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D002843:Chromatin; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D019014:fas Receptor; D004318:Doxycycline