| First Author | Daniel PT | Year | 1999 |
| Journal | Blood | Volume | 94 |
| Issue | 3 | Pages | 1100-7 |
| PubMed ID | 10419903 | Mgi Jnum | J:56692 |
| Mgi Id | MGI:1342186 | Doi | 10.1182/blood.v94.3.1100.415a16_1100_1107 |
| Citation | Daniel PT, et al. (1999) Expression of the death gene Bik/Nbk promotes sensitivity to drug-induced apoptosis in corticosteroid-resistant T-cell lymphoma and prevents tumor growth in severe combined immunodeficient mice. Blood 94(3):1100-7 |
| abstractText | Members of the Bcl-2 gene family have been implicated in the regulation of cell death induced by cytostatic drugs. In some malignancies such as B-cell lymphoma, there is evidence that high expression of Bcl-2 is an independent negative prognostic marker and the overexpression of Bcl-2 has been shown to confer resistance to cytotoxic drugs by preventing drug-induced apoptosis. This function of Bcl-2 can be antagonized by apoptosis-promoting members of the Bcl-2 family. We previously showed that overexpression of Bax restores the chemosensitivity of Bax-deficient breast cancer cell lines. Therefore, we investigated whether the death-promoting Bcl-2 homologue Bik/Nbk can enhance cytostatic drug-induced apoptosis. As a model, we used the T-cell leukemia H9 (CD3(+) and CD4(+)CD8(-)), which is resistant to corticosteroid-induced cell death and does not express endogenous Bik/Nbk. Sensitivity for drug-induced apoptosis was increased 10- to 39-fold in cells transfected with the full-length coding sequence of Bik/Nbk. In addition, apoptosis induced via CD95/Fas or heat shock was increased to a similar extent. These data show that Bik/Nbk, which, unlike Bax, carries only a BH3 but no BH1 or BH2 domain may be a target to enhance chemosensitivity. The complete suppression of tumor growth in a severe combined immunodeficient mouse xenotransplant model suggests that, in analogy to Bax, Bik/Nbk may function as a tumor suppressor gene. |
