Differentiated, cloned rat thyroid epithelial cells (424 cells) were infected with a wild-type and a temperature-sensitive strain of the myeloproliferative variant of the Moloney murine sarcoma virus. The thyroid cells were productively infected and transformed by both virus strains and displayed some of the typical properties of malignant cells, such as morphological changes, growth in soft agar, and in vivo tumorigenicity. The transformation of differentiated cells has provided, in the last few years, a model for studying the correlation between transformed and differentiated phenotypes (1). Most of these studies have been performed on cell systems of mesenchymal origin transformed by acute retroviruses. Very few systems are available of epithelial cells having well-defined biochemical markers of differentiation. A very suitable system for this purpose is represented by the rat thyroid epithelial differentiated cell line (FRT-L cell line). This line consists of epithelial cells which continue to express in vitro the most typical markers of thyroid differentiation (thyroglobulin synthesis and secretion, iodide uptake, and growth dependence on six growth factors including thyrotropin, the physiological thyroid stimulator; 2, 3).We have recently demonstrated that the Kirsten murine sarcoma virus (KiMSV) can transform in vitro undifferentiated as well as differentiated rat thyroid cells of a definite epithelial origin (14, 15). The transformation of these cells is evidenced by morphological criteria, growth in semisolid medium, and tumorigenicity after injection into syngeneic animals (14, 15). Transformation of the differentiated cells is associated with the loss of the markerE of epithelial thyroid differentiation (15). The infection of FRT-L cells with a KiMSV mutant temperature sensitive for transformation is followed by the appearance of the transformation markers and the loss of differentiation at the permissive temperature (33°C); the switch from the permissive to the nonpermissive temperature (39°C) does not cause the reappearance of the differentiated functions, while the transformation markers disappear (10, 37).To verify whether the ability to transform rat thyroid epithelial cells is peculiar to KiMSV or is common to other * Corresponding author. acute retroviruses, we infected thyroid cells with a different murine acute retrovirus. To this purpose we used a variant of the Moloney murine sarcoma virus, the myeloproliferative sarcoma virus (MPSV), which was isolated by Chirigos et al. The results presented here indicate clearly that the MPSV has the abilities to transform epithelial thyroid cells of rat origin in vitro and to inhibit the expression of the differentiated phenotype after transformation. The loss of the differentiated markers is irreversible, since FRT-L cells transformed with an MPSV mutant temperature sensitive for transformation irreversibly lose the differentiated phenotype at both permissive and nonpermissive temperatures. Since the infection of FRT-L cells with this mutant at the non...