bcl-xs Gene therapy induces apoptosis of human mammary tumors in nude mice

Bcl-xs is a dominant negative repressor of Bcl-2 and Bcl-xL, both of which inhibit apoptosis. We used a replication-deficient adenoviral vector to transiently overexpress Bcl-xs in MCF-7 human breast cancer cells, which overexpress Bcl-xL. Infection with this vector induced apoptosis in vitro. We th...

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Bibliographic Details
Published inCancer research (Chicago, Ill.) Vol. 56; no. 9; pp. 1965 - 1969
Main Authors EALOVEGA, M. W, MCGINNIS, P. K, SUMANTRAN, V. N, CLARKE, M. F, WICHA, M. S
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 01.05.1996
Subjects
Animals
Antineoplastic agents
Apoptosis - genetics
bcl-X Protein
Biological and medical sciences
Chemotherapy
Female
Gene Transfer Techniques
Genetic Therapy
Humans
Mammary Neoplasms, Experimental - genetics
Mammary Neoplasms, Experimental - pathology
Mammary Neoplasms, Experimental - therapy
Medical sciences
Mice
Mice, Nude
Neoplasm Transplantation
Pharmacology. Drug treatments
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-bcl-2
Human
Solid tumor
Adenoviridae
Rodentia
Intratumoral administration
Malignant tumor
In vitro
Genetic transfer
Virus
Mammary gland diseases
In vivo
Vertebrata
Experimental disease
Mammalia
Treatment
Mouse
Cell death
Animal
Established cell line
Mammary gland
Gene therapy
Tumor cell
Apoptosis
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Summary:Bcl-xs is a dominant negative repressor of Bcl-2 and Bcl-xL, both of which inhibit apoptosis. We used a replication-deficient adenoviral vector to transiently overexpress Bcl-xs in MCF-7 human breast cancer cells, which overexpress Bcl-xL. Infection with this vector induced apoptosis in vitro. We then determined the effects of intratumoral injection of bcl-xs adenovirus on solid MCF-7 tumors in nude mice. Tumors injected four times with the bcl-xs adenovirus showed a 50% reduction in size. Using terminal transferase-mediated dUTP-digoxigenin nick end labeling, we observed apoptotic cells at sites of bcl-xs adenoviral injection. These experiments demonstrate the feasibility of using bcl-xs gene therapy to induce apoptosis in human breast tumors.
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ISSN:0008-5472
1538-7445