Quantification of mouse mammary tumor virus structural proteins in hormone‐induced mammary tumors of low mammary tumor mouse strains

Abstract

The expression of the mouse mammary tumor virus (MMTV) in hormone-induced mammary tumors was investigated by means of a radioimmunoassay for two major MMTV proteins, gp52 and p27. MMTV proteins were isolated on lectin affinity- and ion-exchange chromatography columns. The purified viral proteins were electrophoretically homogeneous and retained immunoreactivity after labelling with 125iodine. Standard competition assays showed that group-specific antigenic determinants were reacting. Mammary tumors were induced in three strains of mice with a low natural incidence of mammary tumors, C57BL, O20 and C3Hf, by a combined hormone treatment, consisting of hypophyseal isografts and administration of progesterone and estrone. Mammary tumors and mammary glands of hormone-treated animals were extracted and used for competition radioimmunoassays. In general, the tumorigenic hormone treatment resulted in enhanced amounts of MMTV proteins in the mammary glands, compared to the amounts found in lactating mammary glands of untreated animals. The levels of MMTV proteins in the mammary tumors were lower than in the mammary glands.

Lack of induction of murine mammary tumor virus expression in cultured mammary glands treated with chemical carcinogens

“…The findings therefore support the concept that endogenous MuMTV genes do not play an evident role in mammary gland transformation by chemical carcinogens. This indication is an agreement with the previously described absence of elevated expression of MuMTV genes in mammary epithelial cells transformed by non-viral agents (Smith et al, 1978;Michalides et al, 19786, 1979;Dusing-Swartz et al, 1979;Nusse et al, 1980). However, those studies examined MuMTV expression at a stage of transformation that is relatively quite removed from the initial transforming event.…”

“…The lack of induction of MuMTV expression occurs in the cultured mammary glands of the mice that range fully in ability to express the viral genome in vivo. Thus, BALB/c mice make extremely little MuMTV RNA, viral proteins and virions (Varmus et al, 1973;Michalides, 1978a;Dudley et al, 1978b;Long et al, 1980); C57BL/6 mice make MuMTV RNA, but very small amounts of viral proteins and virions (Varmus et al, 1973;Nusse et al, 1980); and C3H mice make all three (Moore et al, 1979). The findings therefore support the concept that endogenous MuMTV genes do not play an evident role in mammary gland transformation by chemical carcinogens.…”

“…Further, neither DMBA nor FAA induced measurable amounts of gp52 in the cultured BALB/c glands. Similarly, glands from C57BL/6 mice, which also do not produce MuMTV proteins in vivo (Long et al, 1980;Nusse et al, 1980), had no detectable gp52 following treatment with either DMBA, FAA or solvent (control) ( Table I). On the other hand, control mammary glands of C3H mice, a strain that does express significant amounts of gp52 in vivo, did have measurable amounts of gp52 in culture (Table I).…”

“…The mammary glands of C3H mice produce considerable amounts of MuMTV in vivo (Moore et al, 1979). In contrast, the glands of C57BL/6 mice synthesize relatively moderate amounts of viral RNA but little or no viral protein (Varmus et al, 1973;Michalides et al, 19786;Long et al, 1980;Nusse et al, 1980). We therefore examined the levels of MuMTV virus-specific RNA in C57BL/6 and C3H mammary glands treated with chemical carcinogens at days 3 to 4 of culturing, and maintained in the development medium for 9 days.…”

“…Despite the elevated transcription of endogenous viral genes found in mammary tumors induced by combined treatments with urethane and X-rays in BALBk mice, little viral protein has been detected (Michalides et al, 1979). Also, increased levels of both viral RNA and protein have been reported to occur in mammary tumors resulting from hormonal stimulation in BALB/c mice (McGrath et al, 1978;Michalides et al, 1979), although not in tumors induced by hormones or chemicals in other strains (Michalides et al, 1978a;Smith et al, 1978;Nusse et al, 1980). In contrast, other investigators have found little or no induction of viral RNA in BALBk mammary tumors caused by non-viral agents, or in the cell lines derived from those tumors (Dudley et al, 1978a;Dusing-Swartz et al, 1979).…”