Thymic tumorigenesis induced by overexpression of p56lck.
The lck gene encodes a membrane-associated protein tyrosine kinase (p56lck) that is believed to participate in lymphocyte-specific signal transduction pathways. To investigate the function of this molecule, transgenic mice were generated carrying the wild-type lck gene or a mutated lck gene encoding a constitutively activated form of p56lck (p56lckF505). Transgene expression in thymocytes was achieved in each case using the lck proximal promoter element. Mice expressing high levels of either p56lckF505 or p56lckY505 reproducibly developed thymic tumors. The sensitivity of thymocytes to p56lck-induced transformation suggests that disturbances in lck expression may contribute to the pathogenesis of some human neoplastic diseases.
Abraham
K M
KM
Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Levin
S D
SD
Marth
J D
JD
Forbush
K A
KA
Perlmutter
R M
RM
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003001:Cloning, Molecular; D015972:Gene Expression Regulation, Neoplastic; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008822:Mice, Transgenic; D009857:Oncogenes; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000473:pathology; D013945:Thymoma / Q000235:genetics*; D013953:Thymus Neoplasms / Q000235:genetics*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)