title: Potential synergism of Bim with p53 in mice with Myc‑induced lymphoma             in a mouse lymphoma model.
abstract: We report that Bim has an apoptotic function through Bax/mitochondrial apoptosis signaling in the p53-independent mode, which is somewhat additive to the effects of p53. Bim-deficient mouse embryonic fibroblast (MEF) cells were resistant to the apoptotic effects of Myc, while loss of Bim accelerated lymphoma development. Furthermore, Bim was overexpressed at the same frequency in Myc-initiated lymphomas, irrespective of p53 status, suggesting that Bim resides in a pathway separate from p53. Loss of Bim further augmented resistance to apoptosis in p53-/- MEFs. Mice with p53 knockdown exhibited exacerbated malignancies in the absence of Bim. The combined loss of these proteins promoted more severe spontaneous tumorigenesis. Thus, Myc-induced apoptotic signals through Bim and p53 must bifurcate to activate Bax, suggesting that the activation of Bim and p53 significantly contribute to apoptosis. Our results, therefore, establish that p53 and Bim are effective key initiators of apoptosis in lymphoma cells, particularly when combined.
authors.affiliation: Department of Pathology, Linyi Municipal Hospital, Linyi, Shandong, People's Republic of China.
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Shang
authors.forename: Dianliang
authors.initials: D
authors.lastname: Zhang
authors.forename: Chunbao
authors.initials: C
authors.lastname: Guo
authors.forename: Qiu
authors.initials: Q
authors.lastname: Lin
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Guo
authors.forename: Chun
authors.initials: C
authors.lastname: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts; D008223:Lymphoma / Q000401:mortality / Q000503:physiopathology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein