Increased detection of specific tyrosine phosphoproteins correlates with tumor progression of Abelson virus-infected lymphocytes.
Leukemias induced with the v-abl or BCR/ABL oncogene undergo a process of tumor progression which suggests that the ABL oncogene is required but not sufficient for full transformation. In order to identify cellular changes that correlate with progression to full transformation in v-abl transformed lymphoblasts Abelson virus (A-MuLV)-infected murine bone marrow was plated over a pre-established stromal feeder layer. Shortly after A-MuLV infection, transformed lymphoblasts were poorly oncogenic, but over time, progressed in a stepwide manner to a more oncogenic state. The transformants first acquired the ability to grow efficiently in agar, but only over the feeder layer. They next progressed to efficient feeder-independent growth in liquid culture, and then to efficient feeder-independent growth in soft agar. Cell lines that reached the advanced stage of feeder-independent agar growth showed increased detection by antiphosphotyrosine Western blot of the GAP-associated p62 phosphoprotein as well as of a 55 kDa phosphoprotein while detection of the P160 v-abl phosphoprotein remained constant throughout all stages of progression. Although the identity of the p55 phosphoprotein and the mechanism by which detection of p55 and p62 phosphoproteins change on the Western blots during tumor progression are unknown, the data demonstrate that these changes strongly correlate with the stage of progression of v-abl-transformed cells and raise the possibility that these changes may play a role in tumor progression in this model.
Department of Human Oncology, University of Wisconsin, School of Medicine, Madison.
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Clark
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Liang
D016475:3T3 Cells; D000011:Abelson murine leukemia virus / Q000235:genetics*; D000818:Animals; D002471:Cell Transformation, Neoplastic; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D007942:Leukemia, Experimental / Q000209:etiology* / Q000378:metabolism; D008214:Lymphocytes / Q000737:chemistry / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000032:analysis*; D016601:RNA-Binding Proteins / Q000032:analysis; D014443:Tyrosine / Q000378:metabolism*
D004268:DNA-Binding Proteins; C489561:Dok1 protein, mouse; C074561:GAP-associated protein p62; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D014443:Tyrosine