581

BAX

BCL2L4;BCL2-associated X protein;BAX;BCL2-associated X protein

BCL2-associated X protein omega|Baxdelta2G9|Baxdelta2G9omega|Baxdelta2omega|apoptosis regulator BAX|bcl-2-like protein 4|bcl2-L-4

19q13.3-q13.4

protein-coding

Changes in expression of protooncogenes and tumor suppressor genes play a key role in oncogenesis. Dysfunction of their protein products leads to abnormal regulation of signaling pathways, which control the cell cycle, apoptosis, genetic stability, cell differentiation, and morphogenetic reactions. Changes in these important physiological processes are obviously responsible both for initial steps of neoplastic cell transformation and for determination of subsequent tumor progression resulting in the development of malignant tumors.

BAX and BAK are essential regulators of proapoptotic signaling, and the disruption of apoptosis is linked to the development of cancer. To investigate the role of BAX and BAK in tumorigenesis, primary baby mouse kidney epithelial cells (BMKs) from wild-type, BAX-, BAK-, or BAK- and BAK-deficient mice were transformed by adenovirus E1A and dominant-negative p53 (p53DD). In wild-type BMKs, the expression of E1A and inactivation of p53 was sufficient for transformation but not tumorigenesis. In contrast, E1A- and p53DD-transformed BAX- and BAK-deficient BMKs formed highly invasive carcinomas. Transformed BMKs deficient for either BAX or BAK were also tumorigenic, but only when heterozygous for the remaining bax or bak allele, the expression of which was lost in most resulting tumors. Thus, BAX and BAK function to suppress tumorigenesis, and their deficiency was selected for in vivo.