Neither loss of Bik alone, nor combined loss of Bik and Noxa, accelerate murine lymphoma development or render lymphoma cells resistant to DNA damaging drugs

Happo, L; Phipson, B; Smyth, GK; Strasser, A; Scott, CL

Author(s): Happo, L; Phipson, B; Smyth, GK; Strasser, A; Scott, CL;
Details: Publication Year 2012-05,Volume 3,Issue #5,Page e306
Journal Title: CELL DEATH & DISEASE
Publication Type: Journal Article
Abstract: The pro-apoptotic BH3-only protein, BIK, is widely expressed and although many critical functions in developmental or stress-induced death have been ascribed to this protein, mice lacking Bik display no overt abnormalities. It has been postulated that Bik can serve as a tumour suppressor, on the basis that its deficiency and loss of apoptotic function have been reported in many human cancers, including lymphoid malignancies. Evasion of apoptosis is a major factor contributing to c-Myc-induced tumour development, but despite this, we found that Bik deficiency did not accelerate E mu-Myc-induced lymphomagenesis. Co-operation between BIK and NOXA, another BH3-only protein, has been previously described, and was attributed to their complementary binding specificities to distinct subsets of pro-survival BCL-2 family proteins. Nevertheless, combined deficiency of Bik and Noxa did not alter the onset of E mu-Myc transgene induced lymphoma development. Moreover, although p53-mediated induction of Bik has been reported, neither E mu-Myc/Bik(-/-) nor E mu-Myc/Bik(-/-) Noxa(-/-) lymphomas were more resistant than control E mu-Myc lymphomas to killing by DNA damaging drugs, either in vitro or in vivo. These results suggest that Bik, even in combination with Noxa, is not a potent suppressor of c-Myc-driven tumourigenesis or critical for chemotherapeutic drug-induced killing of Myc-driven tumours. Cell Death and Disease (2012) 3, e306; doi:10.1038/cddis.2012.42; published online 10 May 2012
Publisher: NATURE PUBLISHING GROUP
Keywords: MYC-INDUCED LYMPHOMAGENESIS; ENDOPLASMIC-RETICULUM; C-MYC; MEMBRANE PERMEABILIZATION; FAMILY PROTEINS; TRANSGENIC MICE; BCL-2 PROTEINS; CANCER-CELLS; DEATH; APOPTOSIS
Research Division(s): Molecular Genetics Of Cancer; Bioinformatics
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366076/
Publisher's Version: https://doi.org/10.1038/cddis.2012.42

Creation Date: 2012-05-01 12:00:00