Loss of viral gene expression and retention of tumorigenicity by Abelson lymphoma cells

Abstract

Lymphomas induced by the Abelson murine leukemia virus (A-MuLV) were examined for the expression of biochemical and biological markers associated with A-MuLV transformation before and after in vivo growth in genetically distinguishable host mice. Although all tumors and clonal lines derived from them initially expressed the A-MuLV-encoded gag fusion protein p160, they ceased synthesis of this molecule after several weeks of growth in vivo as ascites tumors. Transplanted clonal lines continued to express the alloantigenic marker H-2b and the isoenzyme marker Gpi-lb of the donor tumor cells, indicating that the cells were of donor and not host origin. Examination of cellular DNA obtained from p160-positive and derivative p160-negative lines indicated that p160-negative clones had lost A-MuLV-specific proviral sequences as detected by hybridization with several probes. Although the clonal lines no longer expressed p160, they retained their malignant phenotype and continued to express the Abelson antigen, a cell surface marker associated with A-MuLV lymphomagenesis. Continued expression of the A-MuLV genome was not required for maintenance of oncogenic potential under these conditions of in vivo tumor growth.

P80: a tumor-related protein found in many lymphomas of mice.

“…2, lane f). Moreover, nucleic acid hybridization experiments indicated that most, if not all, of the A -M u L V proviral genome was lost from E2F1 cells (19). A similar result was observed when E3 cells were compared with F11A cells, a line derived from E3 after seven in vivo passages.…”

“…We recently observed that continued in vivo propagation of some A-MuLV lymphomas results in the appearance of tumor cells that are different from most A-MuLV lymphoma cells in the expression of the A-MuLVencoded gag-fusion protein (19). Tumor cells recovered after several in vivo passages (p 12-p45) no longer synthesized detectable amounts of the A-MuLV-encoded gagfusion protein p 160, although this protein was readily detectable in earlier transplants (0-5) of the same tumors (32).…”

“…After five in vivo transplants, the t u m o r cells, termed E2F1, were placed back into culture and checked for the presence of H-2 or Gpi-1 markers to determine whether the cells were derived from the donor cell population or from the host. E2F1 cells expressed only the H-2 b antigens and Gpi-1 b isoenzyme characteristic of the donor (19). T h e initial E2 and derivative E2Fx cells were then radiolabeled and examined for synthesis of the A -M u L V gag-fusion protein p160 using anti-gag p15 serum or the p115, p80, p32 molecules detected with anti-p80 t u m o r regressor serum ( Fig.…”

Differentiation of abelson murine leukemia virus‐infected promonocytic leukemia cells

“…Thus, these promonocytic cells present an opportunity to examine the role of viral oncogene expression (v-abl) in maintaining the transformed state. Previous studies of lymphoid cells infected with A-MuLV have shown both increases in oncogenicity without changes in vabl expression and loss of v-abl expression with no change in oncogenicity (Grunwald et al, 1982;Whitlock et al, 19836). It has not yet been demonstrated, however, that differentiation of the A-MuLV-infected promonocyte cells described here is accompanied by an actual reduction in v-abl expression, but rather only that differentiation is accompanied by a reduced production of infectious A-MuLV.…”

“…However, expression of v-abl, the viral oncogene, may not by itself be sufficient for either the production or the maintenance of highly tumorigenic cells. Both loss of v-abl expression without loss of tumorigenicity (Grunwald et al, 1982), and increases in tumorigenicity without detectable changes in the concentration, half-life, phosphorylation, in vitro kinase activity, or cellular localization of the v-abl product (Whitlock et al, 19836) have been reported. These findings, along with the identification of cellular transforming sequences from A-MuLV-induced tumors which are distinct from the v-abl product (Lane et al, 1982), have been interpreted to indicate that v-abl expression may induce early events in the leukemogenic process, but that secondary alterations in expression of cellular genes may be necessary for full expression of leukemogenic potential (Lane et al, 1982;Pillemer et al, 1984;Whitlock et al, 19836).…”