Cell transformation and tumor induction by Abelson murine leukemia virus in the absence of helper virus.

Abstract

We investigated the role of the Moloney helper virus, Moloney murine leukemia virus (Mo-MuLV), in cell transformation and tumor induction by the defective Abelson murine leukemia virus (Ab-MuLV). A molecular clone of Ab-MuLV (P160 strain) was transfected into the tA2 packaging cell line, and helper virus-free Ab-MuLV(qk2) was harvested from the supernatant medium. Ab-MuLV(f2) was as efficient as helper virus-containing Ab-MuLV(Mo-MuLV) in the transformation of primary bone marrow cells in vitro.Inoculation of weanling BALB/c mice with induced nonthymic pre-B-cell lymphomas with high efficiency and short latency (28 days). Adult BALB/c mice were less sensitive to tumor induction by a factor of 100. Ab-MuLV(q2) did not induce tumors in weanling C57BL/6 mice, unlike (24). C57BL/6 nu/nu mice were obtained from Norman Drinkwater (University of Wisconsin) and maintained by brother-sister mating. Mice were anesthetized and inoculated through the retroorbital sinus vein with 0.1-0.5 ml of tissue culture supernatant. Mice were observed three times a week for lymphadenopathy, paraplegia, or cathexia for a period of 3 months after infection.Viruses and Cells. The Ab-MuLV (P160 strain) proviral clone pAB4 was recovered in X CH4A from an Ab-MuLVinduced tumor cell line, E102 (25), DNA library and characterized in our laboratory. Ab-MuLV(Mo-MuLV) was recovered from harvests of supernatant fluids of NIH 3T3 cells cotransfected with 1 Ag of pAB4 and 2 pug of Mo-MuLV-Mov3 (26) proviral clones. Ab-MuLV(qi2) was harvested from supernatants of morphologically transformed cell clones of t2 cells (1) 5932The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Increased Expression of Bcl-xL and c-Myc Is Associated with Transformation by Abelson Murine Leukemia Virus

“…mitogenic signals (3), v-Abl-dependent transformation is also a multi-step process, requiring genetic alterations in addition to expression of the v-Abl oncoprotein. This is suggested by the fact that A-MuLV infects many cell types in vivo but transforms only a limited number of pro-/pre-B cell clones (5,6). Earlier studies provided direct evidence for a multi-step process of v-Abl transformation: after being maintained in culture for 3 months, Abelson-transformed lymphoid cells showed improved growth in liquid culture and caused rapid tumor formation in animals (33).…”

Expression of v-rel induces mature B-cell lines that reflect the diversity of avian immunoglobulin heavy- and light-chain rearrangements.

“…While infection of murine bone marrow and fetal liver with Abelson leukemia virus has been useful in producing murine pre-B-and immature B-cell lines, less than 1% of the original colonies are able to sustain proliferation and become permanent cell lines (15). While fully developed Abelson virus-induced tumors plate with higher but variable efficiency in culture (15), very few of these tumors express IgM (13,14). Similarly, while most Abelson virus-derived lines have rearranged immunoglobulin genes, the frequency with which they express IgM is very low (1,29,34).…”

Inhibition of v-Abl transformation by p53 and p19ARF

“…Primary mouse embryonic ®broblasts (MEFs) are highly resistant to v-Abl transformation. While many cells are initially infected in vivo, v-Abl-induced pre-B cell tumors are usually clonal or oligo clonal, suggesting that rare clones grow out (Green et al, 1987(Green et al, , 1989. Similarly, A-MuLV infected cells passaged in vitro gradually gain higher oncogenic activity by clonal selection.…”