Defective control of terminal differentiation and its role in carcinogenesis in the 3T3 T proadipocyte stem cell line.

ABSTRACT

The expression of defects in the control of terminal cellular differentiation has been implicated to be of etiological significance in the pathogenesis of cancer. However, it has not been established whether or not additional defects in the control of cellular differentiation and proliferation are required for the expression of the completely transformed phenotype. We therefore developed four clones of proadipocyte stem cells that express a single specific defect that limits their capacity to undergo the terminal phase in differentiation. The value of these clones is emphasized by the fact that they show no defects in their ability to regulate nonterminal differentiation or proliferation relative to native nontransformed proadipocyte stem cells. Terminal differentiation-defective clones were therefore assayed to determine if they express the completely transformed phenotype. The results show that differentiation-defective stem cells are not tumorigenic in vivo and do not grow in soft agar, which is an in vitro assay for expression of the transformed phenotype by murine mesenchymal cells. These data are interpreted to support the conclusion that the expression of defects in the control of the terminal phase of differentiation per se is not adequate to induce complete neoplastic transformation.