Cell growth and differentiation of a novel mouse Ito (fat-storing) cell line transformed by a temperature-sensitive mutant of simian virus 40.

A novel mouse Ito (fat-storing) cell line (A640-IS) was established by transformation with a temperature-sensitive mutant of simian virus 40 (SV40) and the relationships between the expression of SV40 large T antigen and the growth, differentiation, and functions of A640-IS cells were investigated. A640-IS cells expressed large T antigen when cultured at 33 degrees C. At this temperature, the cells grew actively, assumed a fibroblastic shape, and showed few Ito cell characteristics. In contrast, when large T-antigen expression was inhibited by culture at 39 degrees C, the cells did not grow but differentiated into Ito cells as assessed by both morphological and functional characteristics. Expression of the transcription factor SCL (stem cell leukemia), which plays a role in the development and differentiation of blood cells, was observed at both 33 degrees C and 39 degrees C, although expression was greater at 33 degrees C. Therefore, opposite patterns of cell growth and the functions of differentiated cells occurred at 33 degrees C and 39 degrees C in this novel Ito cell line. Transforming growth factor beta1 stimulated A640-IS cells to produce fibronectin, collagen type III, and laminin. This unique Ito cell line provides a useful model to address important questions regarding the nature of these cells.