Ink4c is dispensable for tumor suppression in Myc-induced B-cell lymphomagenesis.
p18(Ink4c) functions as a dedicated inhibitor of cyclin-D-dependent kinases. Loss of Ink4c predisposes mice to tumor development and, in a dose-dependent manner, complements the tumor-promoting effects of various oncogenes. We have now addressed whether Ink4c loss impacts B-cell tumor development in the Emu-Myc transgenic mouse, a model of human Burkitt lymphoma. Loss of one or both alleles did not influence the onset of lymphoma in Emu-Myc transgenics, and did not appreciably affect Myc's proliferative or apoptotic responses in precancerous B cells. Nevertheless, Ink4c loss modulated the effects of Myc-induced transformation by decreasing the frequency of Arf loss, an ordinarily common event in Emu-Myc-induced lymphomas.
Nilsson
L M
LM
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Keller
U B
UB
Yang
C
C
Nilsson
J A
JA
Cleveland
J L
JL
Roussel
M F
MF
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D050438:Genes, Immunoglobulin Heavy Chain; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*
C417743:Cdkn2a protein, mouse; C493972:Cdkn2c protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; C489428:Myc protein, mouse; D015514:Oncogene Proteins, Fusion; D016271:Proto-Oncogene Proteins c-myc