Changes in MuMTV DNA and RNA levels in Balb/c mammary epithelial cells during malignant transformation by exogenous MuMTV and by hormones

Abstract

Concentrations of MuMTV sequences in DNA and RNA of normal Balb/c mammary epithelial cells were compared with concentrations in virus- and hormone-induced premalignant and malignant derivatives. Normal mammary cells contained multiple (five or six) copies of MuMTV sequences inDNA. These sequences were present at identical frequencies in nonmammary cells. Malignant mammary cells, transformed after MuMTV-S infection, contained a two- to threefold increase in the number of MuMTV sequence copies in nuclear DNA. These extra MuMTV sequences were not detected in DNA of normal mammary epithelial cells of MuMTV-S-infected females or in MuMTV-S-induced premalignant cells. Neither malignant nor premalignant mammary cells transformed after prolonged exposure to mammotropic hormones contained the additional MuMTV sequences detected in virus-induced malignant cells. MuMTV sequences detected in malignant Balb/c mammary epithelial cells, whether these were transformed after infection by exogenous MuMTV-S or prolonged exposure to mammotropic hormones, were indistinguishable by DNA-cDNA hybrid thermal denaturation from the MuMTV sequences in DNA of normal cells. Steady-state levels of MuMTV RNA maintained in normal mammary epithelial cells varied as a function of physiologic state and age. Lactating cells of young animals contained the highest MuMTV RNA concentrations (ca. 0.003% of cell RNA was MuMTV-specific), and midpregnant cells of young animals contained similar levels of some MuMTV RNA sequences, but disproportionately lower levels of other sequences. Mammary epithelium from aged animals, either midpregnant, lactating or resting, contained the lowest concentrations of MuMTV RNA (less than one 35 S equivalent per cell). Mammary adenocarcinomas induced either by MuMTV-S or by mammotropic hormones contained 30–50-fold higher concentrations of MuMTV RNA than detected in normal mammary cells of young animals, corresponding to approximately 1000 35 S equivalents per cell. Similarly high concentrations were detected in premalignant cells. The MuMTV RNA sequences detected in the malignant and premalignant cells (virus- or hormone-induced) were equally homologous to MuMTV-P cDNA. A minor degree of base mismatching was observed in hybrids formed between MuMTV-P cDNA and RNA from normal Balb/c mammary tissues.