Table 1.

Induced expression of NeuT, an oncogenic version of ERBB-2, causes predominantly antiapoptotic alterations in RNA expression of Bcl-2 family members and proteins interacting with Bcl-2 family members

Symbol (gene)FunctionExpression after induction of NeuT* (fold expression)
6 h12 h24 h3 d14 d
Bcl-2 family members
    MCL-1 (myeloid cell leukemia 1)Antiapoptotic protein of the Bcl-2 family that heterodimerizes with other Bcl-2 family members to protect against apoptotic cell death (37)2.5193.1062.1982.3191.864
    BMF (BCL2-modifying factor)Interaction with prosurvival Bcl-2 family members to trigger apoptosis (38)−1.576−1.590−1.577−1.315−1.205
    BCL2L13 (BCL2-like 13)Inhibits cell death upon growth factor withdrawal similar to Bcl-2 (39)−1.355−1.321−1.279−1.133−1.056
    BNIP1 (BCL2/adenovirus E1B 19-kDa protein-interacting protein 1)BNIP1 variants interact with Bcl-2 and also with Bcl-xL (30, 33)1.9731.8441.5591.7871.052
    BNIP3 (BCL2/adenovirus E1B 19-kDa protein-interacting protein 3)Bcl-2 proapoptotic family member recently shown to induce necrosis rather than apoptosis. Interacts with other Bcl-2 family members (31–33)1.0231.2021.6691.0171.043
    BAX (BCL2-associated X protein)Induces apoptosis by binding to the mitochondrial permeability transition pore complex (37, 40)1.056−1.237−1.204−1.424−1.586
Direct protein interaction with Bcl-2 family members
    BNIPL (BCL2/adenovirus E1B 19-kDa protein-interacting protein 2-like)BCH domain of the BNIPL2 isoform interacts with Bcl-2, proapoptotic function (41)−1.383−2.062−1.814−1.685−2.202
    TEGT (testis-enhanced gene transcript)Interactions between the proteins of the TEGT and the Bcl-2 families, stimulation of the antiapoptotic function of Bcl-2 or inhibition of the proapoptotic effect of BAX (42)0.0120.068−0.0121.5711.545
    CLU (clusterin)Inhibits apoptosis by interfering with BAX (26)1.0501.257−1.013−4.095−4.323
    BECN1 (beclin 1)Beclin interacts with Bcl-2 and BCLXL but not with BAX (22)1.4381.5521.3671.4191.308
    BAG1 (BCL2-associated athanogene 1)Binds to Bcl-2, prevents fibroblasts from undergoing apoptosis (43, 44)1.6542.0201.5581.0891.088

NOTE: NeuT was expressed in MCF-7 breast cancer cells in a doxycycline-dependent manner using the Tet-on system. RNA from MCF-7 cells was harvested 6, 12, and 24 h as well as 3 and 14 d after onset of exposure to doxycycline and analyzed by Affymetrix gene array. Three independent batches of MCF-7 cells were analyzed, in which the cells were cultured for at least two passages between the individual experiments and doxycycline incubations, as well as RNA isolations which were done at different days. Expression data are medians of the corresponding probe sets. We summarized all Bcl-2 family members and all factors directly interacting with Bcl family members that were upregulated or downregulated by a factor of at least 1.5 as a consequence of induced NeuT overexpression.

  • *Expression of MCF-7 cells not exposed to doxycycline was used as a control and corresponds to a gene expression of 1.0.