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
AuthorHappo, L; Phipson, B; Smyth, GK; Strasser, A; Scott, CL
Source TitleCell Death and Disease
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sPHIPSON, BELINDA; Smyth, Gordon; Strasser, Andreas; Scott, Clare; HAPPO, LINA
AffiliationSchool of Mathematics and Statistics
Medical Biology (W.E.H.I.)
Obstetrics and Gynaecology
Document TypeJournal Article
CitationsHappo, L., Phipson, B., Smyth, G. K., Strasser, A. & Scott, C. L. (2012). 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. CELL DEATH & DISEASE, 3 (5), https://doi.org/10.1038/cddis.2012.42.
Access StatusOpen Access
NHMRC Grant codeNHMRC/461221
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 Eμ-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 Eμ-Myc transgene induced lymphoma development. Moreover, although p53-mediated induction of Bik has been reported, neither Eμ-Myc/Bik(-/-) nor Eμ-Myc/Bik(-/-)Noxa(-/-) lymphomas were more resistant than control Eμ-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.
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