A recombinant bcl-x s adenovirus selectively induces apoptosis in cancer cells but not in normal bone marrow cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 24; pp. 11024 - 11028
• Main Authors: Clarke, M F, Apel, I J, Benedict, M A, Eipers, P G, Sumantran, V, González-García, M, Doedens, M, Fukunaga, N, Davidson, B, Dick, J E, Minn, A J, Boise, L H, Thompson, C B, Wicha, M, Núñez, G
• Format: Journal Article
• Language: English
• Published: United States National Acad Sciences 21-11-1995
• Subjects: Adenoviruses, Human - genetics; Animals; Apoptosis; bcl-X Protein; Bone Marrow Cells; Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Humans; Mice; Mice, SCID; Neoplasms - genetics; Neoplasms - pathology; Neoplasms - therapy; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-bcl-2; Recombinant Proteins; Transplantation, Heterologous; Tumor Cells, Cultured
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.24.11024

Many cancers overexpress a member of the bcl-2 family of inhibitors of apoptosis. To determine the role of these proteins in maintaining cancer cell viability, an adenovirus vector that expresses bcl-xs, a functional inhibitor of these proteins, was constructed. Even in the absence of an exogenous apoptotic signal such as x-irradiation, this virus specifically and efficiently kills carcinoma cells arising from multiple organs including breast, colon, stomach, and neuroblasts. In contrast, normal hematopoietic progenitor cells and primitive cells capable of repopulating severe combined immunodeficient mice were refractory to killing by the bcl-xs adenovirus. These results suggest that Bcl-2 family members are required for survival of cancer cells derived from solid tissues. The bcl-xs adenovirus vector may prove useful in killing cancer cells contaminating the bone marrow of patients undergoing autologous bone marrow transplantation.