Effect of antineoplastic drugs on the expression of Bcl-2 and Bcl-xL genes in the feline T-cell leukemia cell line.
The Bcl-2 gene is the first member of a rapidly expanding family of genes that regulate apoptosis. Bcl-2 has been shown to repress cell death triggered by a diverse array of stimuli including chemotherapy and gamma-irradiation. Chemotherapy of feline lymphoma is generally carried out with antineoplastic drugs, which are reported to induce apoptosis in tumor cells. However, the precise apoptotic signals, induced by chemotherapeutic drugs against feline tumors have not been fully characterized. Therefore, we have evaluated the expression of Bcl-2 and Bcl-xL in FT-1 upon in vitro treatment with these drugs. In the present study, full length of feline Bcl-xL gene was sequenced, and the expressions of Bcl-2 and Bcl-xL mRNAs in feline lymphoma cell line (FT-1) cultured with doxorubicin, prednisolone or vincristine were investigated. Feline Bcl-xL clone was 1163 base pairs in length and encoded 233 amino acids. The predicted amino acid sequence was 99.1%, 98.7%, 96.1%, 97.4%, 97.0% and 97.9% homologous to predicted Bcl-xL of dog, human, mouse, pig, rat and sheep, respectively. The levels of Bcl-2 transcripts at 24h incubation in FT-1 stimulated with doxorubicin (0.3mug/ml), prednisolone (0.2mug/ml) and vincristine (5ng/ml) were increased to about 41.0-, 62.0- and 11.1-fold to those in non-stimulated FT-1, respectively. On the other hand, the level of Bcl-xL transcripts at 24h incubation in FT-1 stimulated by doxorubicin and prednisolone were significantly increased about 4.2- and 5.8-folds to the controls and inducible level of Bcl-xL by vincristine was decreased about 0.35-folds.
Sano
Junichi
J
Department of Pathobiology, Nihon University School of Veterinary Medicine, 1866, Kameino, Fujisawa, Kanagawa, 252-8510, Japan.
Nagafuchi
Shunpei
S
Yamazaki
Junpei
J
Oguma
Keisuke
K
Kano
Rui
R
Hasegawa
Atsuhiko
A
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002415:Cats; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000235:genetics* / Q000662:veterinary*; D008969:Molecular Sequence Data; D011239:Prednisolone / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014750:Vincristine / Q000494:pharmacology; D051020:bcl-X Protein / Q000235:genetics*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D014750:Vincristine; D004317:Doxorubicin; D011239:Prednisolone